CN117761178A - Method for analyzing content of disodium edetate in budesonide suspension for inhalation - Google Patents
Method for analyzing content of disodium edetate in budesonide suspension for inhalation Download PDFInfo
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- 239000000725 suspension Substances 0.000 title claims abstract description 127
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 title claims abstract description 87
- 229960004436 budesonide Drugs 0.000 title claims abstract description 87
- 238000000034 method Methods 0.000 title claims abstract description 40
- ZGTMUACCHSMWAC-UHFFFAOYSA-L EDTA disodium salt (anhydrous) Chemical compound [Na+].[Na+].OC(=O)CN(CC([O-])=O)CCN(CC(O)=O)CC([O-])=O ZGTMUACCHSMWAC-UHFFFAOYSA-L 0.000 title claims abstract 5
- 238000000926 separation method Methods 0.000 claims abstract description 84
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- 150000001875 compounds Chemical class 0.000 claims abstract description 58
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- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 50
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- 239000012071 phase Substances 0.000 claims description 150
- 239000000523 sample Substances 0.000 claims description 146
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- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- VDZOOKBUILJEDG-UHFFFAOYSA-M tetrabutylammonium hydroxide Chemical compound [OH-].CCCC[N+](CCCC)(CCCC)CCCC VDZOOKBUILJEDG-UHFFFAOYSA-M 0.000 description 2
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- AJDUTMFFZHIJEM-UHFFFAOYSA-N n-(9,10-dioxoanthracen-1-yl)-4-[4-[[4-[4-[(9,10-dioxoanthracen-1-yl)carbamoyl]phenyl]phenyl]diazenyl]phenyl]benzamide Chemical compound O=C1C2=CC=CC=C2C(=O)C2=C1C=CC=C2NC(=O)C(C=C1)=CC=C1C(C=C1)=CC=C1N=NC(C=C1)=CC=C1C(C=C1)=CC=C1C(=O)NC1=CC=CC2=C1C(=O)C1=CC=CC=C1C2=O AJDUTMFFZHIJEM-UHFFFAOYSA-N 0.000 description 1
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Abstract
The invention relates to the field of medicines, and discloses a method for analyzing the content of disodium edetate in budesonide suspension for inhalation, which comprises the following steps: preparing a suspension sample for adjusting instrument parameters of a high performance liquid chromatography instrument, constructing a mobile phase in a liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of a high pressure pump and the chromatographic column attribute of a chromatographic column; determining mobile phase parameters, high-pressure pump parameters and chromatographic column parameters of the high-performance liquid chromatographic instrument from mobile phase attributes, high-pressure pump attributes and chromatographic column attributes based on the spectral peak separation degree; constructing a compound band of the compound to be analyzed separated from the budesonide suspension for inhalation in a chromatographic column; analyzing the chromatographic peak area in the compound band by using a detector, and calculating the disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area.
Description
Technical Field
The invention relates to the field of medicines, in particular to a method for analyzing the content of disodium edetate in budesonide suspension for inhalation.
Background
The budesonide suspension for inhalation is mainly used for the treatment of non-glucocorticoid dependent or dependent bronchial asthma and chronic bronchitis, and can replace or reduce oral steroid treatment, a certain amount of disodium edentate (EDTA-2 Na for short) is added into the prescription of the budesonide suspension for inhalation to be used as a metal chelating agent, and the budesonide suspension plays an antioxidant and stabilizing role in a pharmaceutical preparation, and because disodium edentate is easy to chelate with calcium, hypocalcemia can be caused by long-term large-dose use, and therefore, the addition amount of disodium edentate needs to be controlled.
The content determination methods of edetate disodium in the pharmacopoeia of various countries are complexometric titration methods (volumetric method), so that accurate determination of the content of trace edetate disodium cannot be realized, and in addition, the auxiliary materials in the product prescription are more in variety, certain interference can be generated on the specificity of the titration method, and quality control is not facilitated. Therefore, the determination accuracy of the edetate disodium content is insufficient because the specificity of the titration method is easily disturbed.
Disclosure of Invention
In order to solve the problems, the invention provides a method for analyzing the content of disodium edetate in a budesonide suspension for inhalation, which can improve the accuracy of measuring the content of disodium edetate.
In a first aspect, the present invention provides a method for analysing the disodium edetate content of a budesonide suspension for inhalation, comprising:
the method comprises the steps of obtaining a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, wherein the high performance liquid chromatography instrument comprises a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator and a detector;
preparing a suspension sample for adjusting instrument parameters of the high performance liquid chromatography instrument, constructing a mobile phase in the liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of the high pressure pump and the chromatographic column attribute of the chromatographic column;
determining mobile phase parameters, high-pressure pump parameters and chromatographic column parameters of the high-performance liquid chromatographic instrument from the mobile phase attributes, the high-pressure pump attributes and the chromatographic column attributes based on the spectrum peak separation degree;
storing the inhalation budesonide suspension into the sample injector, and based on the high pressure pump parameters, transmitting the regulated mobile phase from the liquid storage tank into the sample injector by the high pressure pump, in the sample injector, transmitting the inhalation budesonide suspension into the chromatographic column through the regulated mobile phase according to the mobile phase parameters, and constructing a compound band of a compound to be analyzed separated from the inhalation budesonide suspension in the chromatographic column based on the chromatographic column parameters and the regulated mobile phase;
Analyzing the chromatographic peak area in the compound band by using the detector, and calculating the disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area.
In one possible implementation manner of the first aspect, the preparing a suspension sample for adjusting an instrument parameter of the high performance liquid chromatography instrument includes:
collecting a concentration diluent and a sample to be diluted;
calculating the diluent dosage when the concentration diluent carries out gradient dilution on the sample to be diluted;
based on the dosage of the diluent, carrying out gradient dilution on the sample to be diluted by using the concentration diluent to obtain a gradient diluted sample;
inputting the gradient diluted sample into the high performance liquid chromatography instrument to output chromatographic peaks of edetate disodium in the gradient diluted sample through the high performance liquid chromatography instrument;
and when the chromatographic peak is not a preset flat peak, utilizing a corresponding gradient dilution sample in the gradient dilution samples of the chromatographic peak as the suspension sample.
In one possible implementation manner of the first aspect, the calculating the diluent amount when the concentration diluent performs gradient dilution on the sample to be diluted includes:
Calculating the diluent dosage when the concentration diluent is used for carrying out gradient dilution on the sample to be diluted by using the following formula:
wherein m is 2 Represents the diluent amount, m 1 Representing the weight of the sample to be diluted, and determining the weight of the sample to be diluted according to the size of a sample storage space of a sample injector of the high performance liquid chromatography instrument, wherein ρ 1 Representing the concentration of the sample to be diluted ρ 2 And p represents the dilution factor when the concentration diluent is used for carrying out gradient dilution on the sample to be diluted.
In a possible implementation manner of the first aspect, the constructing a mobile phase in the liquid storage tank includes:
constructing a buffer solution and an organic phase in the liquid storage tank;
taking a mixed solution between the buffer solution and the organic phase as an initial mobile phase based on the volume ratio between the buffer solution and the organic phase;
and regulating the pH value of the initial mobile phase to obtain the mobile phase in the liquid storage tank.
In one possible implementation manner of the first aspect, the calculating a spectral peak separation degree of disodium edentate in the suspension sample based on a mobile phase attribute of the mobile phase, a high pressure pump attribute of the high pressure pump, and a chromatographic column attribute of the chromatographic column includes:
Dividing the range of the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump and the attribute value of the chromatographic column attribute of the chromatographic column to obtain a divided range attribute;
constructing a sample chromatographic peak of the suspension sample based on the split range attribute;
calculating the spectral peak separation degree in the sample chromatographic peak by using the following formula:
wherein q represents the spectral peak separation degree, x 2 Representing the sample chromatographic peak, x, of the disodium edentate in the suspension sample in the sample chromatographic peak 1 Representing a sample chromatographic peak adjacent to the sample chromatographic peak corresponding to disodium edentate, y 2 Indicating the low width of the chromatographic peak of the sample corresponding to disodium edentate, y 1 Indicating the low width of the sample chromatographic peak adjacent to the sample chromatographic peak corresponding to disodium edentate.
In a possible implementation manner of the first aspect, the determining, based on the spectral peak separation degree, a mobile phase parameter, a high pressure pump parameter, and a chromatographic column parameter of the high performance liquid chromatography apparatus from the mobile phase attribute, the high pressure pump attribute, and the chromatographic column attribute includes:
extracting a maximum spectral peak separation from the spectral peak separation;
obtaining a target range attribute corresponding to the maximum spectral peak separation degree in a dividing range attribute corresponding to the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute;
Constructing a relation model between the maximum spectrum peak separation degree and the target range attribute;
and selecting mobile phase parameters, high-pressure pump parameters and chromatographic column parameters which can enable the maximum spectral peak separation degree to reach the upper separation degree limit from the target range attribute based on the relation model.
In a possible implementation manner of the first aspect, the constructing a relationship model between the maximum spectral peak separation degree and the target range attribute includes:
constructing a relation model between the maximum spectral peak separation degree and the target range attribute by using the following formula:
wherein,representing the relation model, alpha representing the chromatographic column performance in the target range property, beta representing the compound separation performance between the mobile phase in the target range property and the stationary phase in the chromatographic column, gamma representing the capacity factor between the mobile phase in the target range property and the stationary phase in the chromatographic column, q' representing the maximum spectral peak separation.
In one possible implementation manner of the first aspect, the analyzing, with the detector, a chromatographic peak area in the compound band includes:
converting the compound band to a chromatogram using the detector;
The chromatographic peak area in the chromatogram was calculated using the following formula:
wherein S represents the chromatographic peak area, f (t) represents the time on the abscissa and the curve function in the chromatogram of the response signal of the compound band to the detector on the ordinate, t 1 ～t 2 Representing the duration of the chromatographic peak in the chromatogram.
In one possible implementation manner of the first aspect, the calculating the disodium edentate content of the disodium edentate in the compound to be analyzed according to the chromatographic peak area includes:
calculating disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area by using the following formula:
wherein Cr represents the disodium edentate content, ar represents the chromatographic peak area, cx represents the disodium edentate content of the standard control group, and Ax represents the chromatographic peak area of the standard control group.
In a second aspect, the present invention provides a system for analysis of disodium edetate content in a budesonide suspension for inhalation, the system comprising:
the material acquisition module is used for acquiring a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, wherein the high performance liquid chromatography instrument comprises a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator and a detector;
The separation degree calculation module is used for preparing a suspension sample for adjusting instrument parameters of the high performance liquid chromatography instrument, constructing a mobile phase in the liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of the high pressure pump and the chromatographic column attribute of the chromatographic column;
a parameter determining module, configured to determine a mobile phase parameter, a high pressure pump parameter, and a chromatographic column parameter of the high performance liquid chromatography apparatus from the mobile phase attribute, the high pressure pump attribute, and the chromatographic column attribute based on the peak separation degree;
a band build module for storing the budesonide suspension for inhalation into the sample injector and emitting the regulated mobile phase from the reservoir into the sample injector with the high pressure pump based on the high pressure pump parameter, in the sample injector, the budesonide suspension for inhalation is transported into the chromatographic column by the regulated mobile phase according to the mobile phase parameter, in the chromatographic column, a compound band of a compound to be analyzed separated from the budesonide suspension for inhalation is built based on the chromatographic column parameter and the regulated mobile phase;
And the content calculation module is used for analyzing the chromatographic peak area in the compound band by using the detector and calculating the disodium edentate content of the disodium edentate in the compound to be analyzed according to the chromatographic peak area.
Compared with the prior art, the technical principle and beneficial effect of this scheme lie in:
according to the embodiment of the invention, suspension samples for adjusting instrument parameters of the high performance liquid chromatography instrument are prepared to prepare a plurality of inhalation budesonide suspensions with different concentrations, so that the inhalation budesonide suspensions are utilized to output the chromatograms of disodium edetate in the plurality of inhalation budesonide suspensions with different concentrations, the chromatograms of disodium edetate are used for reversely analyzing which concentrations of the inhalation budesonide suspensions have better edetate separation effect, and the inhalation budesonide suspensions with proper concentrations are finally selected, further, the embodiment of the invention constructs a mobile phase in the liquid storage tank to be used for carrying a sample to be analyzed to a chromatographic column by using the mobile phase later, and separating different compound components in the sample to be analyzed, according to the embodiment of the invention, the spectral peak separation degree of disodium edentate in the suspension sample is calculated based on the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump and the chromatographic column attribute of the chromatographic column, so that the spectral peak separation degree of disodium edentate under the mobile phase attribute of different sizes, the high-pressure pump attribute of different sizes and the chromatographic column attribute of different sizes is observed, when the spectral peak separation degree of disodium edentate is better, the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute which can improve the spectral peak separation degree are selected from a plurality of mobile phase attributes of different sizes, the high-pressure pump attribute and the chromatographic column attribute of different sizes, the subsequent disodium edentate content was calculated using the chromatographic peak area. Therefore, the analysis method of the content of the disodium edetate in the budesonide suspension for inhalation provided by the embodiment of the invention can improve the accuracy of measuring the content of the disodium edetate.
Drawings
The accompanying drawings, which are incorporated in and constitute a part of this specification, illustrate embodiments consistent with the invention and together with the description, serve to explain the principles of the invention.
In order to more clearly illustrate the embodiments of the invention or the technical solutions of the prior art, the drawings which are used in the description of the embodiments or the prior art will be briefly described, and it will be obvious to a person skilled in the art that other drawings can be obtained from these drawings without inventive effort.
FIG. 1 is a flow chart of a method for analyzing the disodium edetate content of a budesonide suspension for inhalation according to an embodiment of the present invention;
FIG. 2a is a schematic diagram of a high performance liquid chromatography apparatus for analyzing the disodium edentate content of the budesonide suspension for inhalation according to an embodiment of the present invention;
FIG. 2b is a schematic diagram showing the chromatographic column and detector interfacing of the method for analyzing the disodium edentate content of the budesonide suspension for inhalation according to an embodiment of the present invention;
FIG. 3 is a schematic diagram showing the flat peaks of the method for analyzing the disodium edentate content of the budesonide suspension for inhalation according to an embodiment of the present invention;
Fig. 4 is a schematic block diagram of an analysis system for disodium edetate content in a budesonide suspension for inhalation according to an embodiment of the present invention.
Detailed Description
It should be understood that the detailed description is presented by way of example only and is not intended to limit the invention.
The embodiment of the invention provides a method for analyzing the content of disodium edetate in a budesonide suspension for inhalation, and an execution subject of the method for analyzing the content of disodium edetate in the budesonide suspension for inhalation comprises, but is not limited to, at least one of a server, a terminal and other electronic equipment capable of being configured to execute the method provided by the embodiment of the invention. In other words, the analysis method of disodium edetate content in the budesonide suspension for inhalation may be performed by software or hardware installed in the terminal equipment or the server equipment, and the software may be a blockchain platform. The service end includes but is not limited to: a single server, a server cluster, a cloud server or a cloud server cluster, and the like. The server may be an independent server, or may be a cloud server that provides cloud services, cloud databases, cloud computing, cloud functions, cloud storage, network services, cloud communications, middleware services, domain name services, security services, content delivery networks (Content Delivery Network, CDN), and basic cloud computing services such as big data and artificial intelligence platforms.
Referring to fig. 1, a flow chart of a method for analyzing the content of disodium edetate in a budesonide suspension for inhalation according to an embodiment of the invention is shown. Wherein, the analysis method of the disodium edetate content in the budesonide suspension for inhalation depicted in figure 1 comprises the following steps:
s1, acquiring a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, wherein the high performance liquid chromatography instrument comprises a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator and a detector.
In the embodiment of the invention, the budesonide suspension for inhalation refers to non-halogenated glucocorticoid, can resist inflammation, allergy, itching and exudation, and relieve high reactivity of respiratory tract and bronchospasm, and a certain amount of disodium edetate (EDTA-2 Na for short) is added into the prescription of the budesonide suspension for inhalation to be used as a metal chelating agent, and further, the high performance liquid chromatography instrument refers to an instrument device which uses a high performance liquid chromatography principle and is mainly used for analyzing organic compounds with high boiling point, difficult volatilization due to heat and large molecular weight.
Referring to fig. 2a, a schematic diagram of a high performance liquid chromatography apparatus for analyzing the disodium edentate content of the budesonide suspension for inhalation according to an embodiment of the invention is shown in fig. 1. In fig. 2a, a liquid storage tank is used for storing a mobile phase, the mobile phase refers to a substance carrying a sample to be measured and moving forward in a chromatographic process, a high-pressure pump refers to a device for providing high-pressure power, so that the mobile phase flows out of the liquid storage tank, a sample injector is used for receiving the sample to be measured and the mobile phase, it is required that the mobile phase continuously flows forward in the sample injector, the sample to be measured is carried with the mobile phase in the flowing process and also flows forward, a stationary phase contained in the mobile phase and a chromatographic column can separate different component substances contained in the sample to be measured from the sample to be measured, the different component substances separated from the sample to be measured are converged into a plurality of different color bands with different dyes in the chromatographic column, and a constant temperature box is used for controlling column temperature of the chromatographic column, so that the different component substances contained in the sample to be measured and indistinguishable by naked eyes are expressed through different chromatograms.
Referring to fig. 2b, a schematic diagram of a chromatographic column and a detector interface of the method for analyzing the disodium edentate content of the budesonide suspension for inhalation according to an embodiment of the present invention is shown in fig. 1. In fig. 2b, HPLC Column represents the chromatographic Column, 1 represents the band of the separation compound characterized by the blue dye, 2 represents the band of the separation compound characterized by the red dye, 3 represents the band of the separation compound characterized by the yellow dye, injection start represents the starting point of the curve in the chromatogram, base-line represents the baseline.
S2, preparing a suspension sample for adjusting instrument parameters of the high performance liquid chromatography instrument, constructing a mobile phase in the liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of the high pressure pump and the chromatographic column attribute of the chromatographic column.
According to the embodiment of the invention, the suspension samples for adjusting the instrument parameters of the high performance liquid chromatography instrument are prepared and used for preparing a plurality of inhalation budesonide suspensions with different concentrations, so that the chromatograms of disodium edetate in the inhalation budesonide suspensions with different concentrations are output by utilizing the inhalation budesonide suspensions, the chromatograms of the disodium edetate are used for reversely analyzing which concentrations of disodium edetate in the inhalation budesonide suspensions have better separation effect, and the inhalation budesonide suspensions with proper concentrations are finally selected.
The instrument parameters comprise a parameter value contained in a mobile phase, a parameter value contained in a high-pressure pump and a parameter value contained in a chromatographic column, and the suspension sample is a solution obtained by mixing a concentration diluent with a budesonide suspension for inhalation.
In one embodiment of the invention, the preparing a suspension sample for adjusting an instrument parameter of the high performance liquid chromatography instrument comprises: collecting a concentration diluent and a sample to be diluted; calculating the diluent dosage when the concentration diluent carries out gradient dilution on the sample to be diluted; based on the dosage of the diluent, carrying out gradient dilution on the sample to be diluted by using the concentration diluent to obtain a gradient diluted sample; inputting the gradient diluted sample into the high performance liquid chromatography instrument to output chromatographic peaks of edetate disodium in the gradient diluted sample through the high performance liquid chromatography instrument; and when the chromatographic peak is not a preset flat peak, utilizing a corresponding gradient dilution sample in the gradient dilution samples of the chromatographic peak as the suspension sample.
The sample to be diluted refers to budesonide suspension for inhalation, the concentration diluent can be replaced by copper acetate, and the chromatographic peak refers to a peak value in a chromatogram outputted by a detector of the high performance liquid chromatography instrument.
Referring to fig. 3, a schematic diagram of flat peaks of an analysis method of disodium edentate content in a budesonide suspension for inhalation according to an embodiment of the present invention is provided in fig. 1. In fig. 3, the broad peak position is the flat peak.
Optionally, the process of performing gradient dilution on the sample to be diluted by using the concentration diluent to obtain a gradient diluted sample includes: and respectively carrying out 10-time dilution, 100-time dilution, 1000-time dilution and the like on the sample to be diluted by using the concentration diluent of the diluent dosage.
When the chromatographic peak is a preset flat peak, the chromatographic peak is beyond the range of the chromatogram detected by the detector of the high performance liquid chromatography instrument, which indicates that the concentration of the gradient diluted sample cannot be used as the concentration of the input sample of the high performance liquid chromatography instrument.
In yet another embodiment of the present invention, the calculating the diluent amount when the concentration diluent performs gradient dilution on the sample to be diluted includes: calculating the diluent dosage when the concentration diluent is used for carrying out gradient dilution on the sample to be diluted by using the following formula:
wherein m is 2 Represents the diluent amount, m 1 Representing the weight of the sample to be diluted, and determining the weight of the sample to be diluted according to the size of a sample storage space of a sample injector of the high performance liquid chromatography instrument, wherein ρ 1 Representing the concentration of the sample to be diluted ρ 2 And p represents the dilution factor when the concentration diluent is used for carrying out gradient dilution on the sample to be diluted.
Further, the mobile phase in the liquid storage tank is constructed for carrying the sample to be analyzed to the chromatographic column by using the mobile phase, and different compound components in the sample to be analyzed are separated.
In one embodiment of the present invention, the constructing the mobile phase in the liquid storage tank includes: constructing a buffer solution and an organic phase in the liquid storage tank; taking a mixed solution between the buffer solution and the organic phase as an initial mobile phase based on the volume ratio between the buffer solution and the organic phase; and regulating the pH value of the initial mobile phase to obtain the mobile phase in the liquid storage tank.
Optionally, the process of constructing the buffer solution and the organic phase in the liquid storage tank is as follows: tetrabutylammonium hydroxide is used as the buffer solution, and acetonitrile is used as the organic phase; the volume ratio between the buffer and the organic phase may be set to (60-90): (40-10); the process for adjusting the pH value of the initial mobile phase comprises the following steps: the pH value of the mobile phase is adjusted by inorganic acid, such as at least one of inorganic acid of hydrochloric acid, phosphoric acid, acetic acid, formic acid, etc., preferably phosphoric acid, and the pH value of the mobile phase is adjusted to be 1.0-5.0, preferably 2.0-4.0.
Further, according to the embodiment of the invention, the spectral peak separation degree of disodium edentate in the suspension sample is calculated based on the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump and the chromatographic column attribute of the chromatographic column, so that the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute which can improve the spectral peak separation degree can be selected from a plurality of mobile phase attributes of different sizes, the high-pressure pump attribute of different sizes and the chromatographic column attribute of different sizes when the spectral peak separation degree of disodium edentate is good.
Wherein the mobile phase property comprises concentration, volume, etc., the high pressure pump property comprises pressure magnitude, and the chromatographic column property comprises concentration of stationary phase, column temperature, etc.
In an embodiment of the present invention, the calculating the peak separation of edetate disodium in the suspension sample based on the mobile phase property of the mobile phase, the high pressure pump property of the high pressure pump, and the column property of the column comprises: dividing the range of the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump and the attribute value of the chromatographic column attribute of the chromatographic column to obtain a divided range attribute; constructing a sample chromatographic peak of the suspension sample based on the split range attribute; calculating the spectral peak separation degree in the sample chromatographic peak by using the following formula:
Wherein q represents the spectral peak separation degree, x 2 Representing the sample chromatographic peak, x, of the disodium edentate in the suspension sample in the sample chromatographic peak 1 Representing a sample chromatographic peak adjacent to the sample chromatographic peak corresponding to disodium edentate, y 2 Indicating the low width of the chromatographic peak of the sample corresponding to disodium edentate, y 1 Indicating the low width of the sample chromatographic peak adjacent to the sample chromatographic peak corresponding to disodium edentate.
Illustratively, the process of dividing the range of the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump, and the attribute value of the chromatographic column attribute of the chromatographic column to obtain the divided range attribute is as follows: when the mobile phase is the concentration of the mobile phase, the high-pressure pump is the pressure, and the chromatographic column is the column temperature, if the concentration of the mobile phase is 1-10, the pressure is 15-20, and the column temperature is 25-30, 1-10 is divided into 1-5 and 6-10 ranges, 15-20 is divided into 15-17 and 18-20 ranges, 25-30 is divided into 25-27 and 28-30 ranges, and the ranges are randomly combined (are attribute combinations among different types of attributes), such as combinations among 1-5, 15-17, 25-27, and 25-27, which are the divided range attributes), from any selected range of 1-5 and 6-10 ranges, 15-17 and 18-20 ranges, and 25-27 ranges, respectively.
The process of constructing the sample chromatographic peak of the suspension sample based on the partitioning range attribute is as follows: taking the average value of the mobile phase range attribute, the average value of the high-pressure pump range attribute and the average value of the chromatographic column range attribute in the dividing range attribute respectively, taking the taken average value as the value of the instrument parameter of the high-performance liquid chromatograph, and then utilizing the detector to realize the chromatographic peak of the suspension sample on the premise of the instrument parameter.
And S3, determining mobile phase parameters, high-pressure pump parameters and chromatographic column parameters of the high-performance liquid chromatographic instrument from the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute based on the spectral peak separation degree.
In an embodiment of the present invention, the determining mobile phase parameters, high pressure pump parameters, and column parameters of the hplc instrument from the mobile phase attribute, the high pressure pump attribute, and the column attribute based on the peak separation degree includes: extracting a maximum spectral peak separation from the spectral peak separation; obtaining a target range attribute corresponding to the maximum spectral peak separation degree in a dividing range attribute corresponding to the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute; constructing a relation model between the maximum spectrum peak separation degree and the target range attribute; and selecting mobile phase parameters, high-pressure pump parameters and chromatographic column parameters which can enable the maximum spectral peak separation degree to reach the upper separation degree limit from the target range attribute based on the relation model.
Optionally, based on the relation model, selecting mobile phase parameters, high-pressure pump parameters and chromatographic column parameters which can enable the maximum spectral peak separation degree to reach the upper separation degree limit from the target range attributes, wherein the processes comprise: and in the relation model, when the input is the average value in the target range attribute, outputting the maximum spectrum peak separation degree, and then continuously selecting attribute values which are larger or smaller than the average value from the target range attribute, and inputting the attribute values into the relation model, so that the adjustment of the increase or decrease of the maximum spectrum peak separation degree is realized.
In yet another embodiment of the present invention, the constructing a relationship model between the maximum spectral peak separation and the target range property includes: constructing a relation model between the maximum spectral peak separation degree and the target range attribute by using the following formula:
wherein,representing the relation model, alpha representing the chromatographic column performance in the target range property, beta representing the compound separation performance between the mobile phase in the target range property and the stationary phase in the chromatographic column, gamma representing the capacity factor between the mobile phase in the target range property and the stationary phase in the chromatographic column, q' representing the maximum spectral peak separation.
The chromatographic column performance is influenced by the composition of the mobile phase and the pressure (the flow rate of the mobile phase can be influenced), the compound separation performance is influenced by the composition of the mobile phase, the composition of the stationary phase and the column temperature, and the capacity factor refers to the mass ratio of the separable components distributed in the stationary phase and the mobile phase when the two phases (the stationary phase and the mobile phase) are distributed to be balanced under certain temperature and pressure.
S4, storing the budesonide suspension for inhalation into the sample injector, and based on the high-pressure pump parameters, transmitting the regulated mobile phase from the liquid storage tank into the sample injector by using the high-pressure pump, wherein the budesonide suspension for inhalation is transmitted into the chromatographic column through the regulated mobile phase according to the mobile phase parameters, and a compound band of a compound to be analyzed separated from the budesonide suspension for inhalation is constructed in the chromatographic column based on the chromatographic column parameters and the regulated mobile phase.
S5, analyzing chromatographic peak areas in the compound band by using the detector, and calculating the disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak areas.
Embodiments of the present invention utilize the detector to analyze the chromatographic peak area in the compound band for calculating a subsequent disodium edentate content based on a correlation between the chromatographic peak area and the subsequent disodium edentate content.
In one embodiment of the invention, the analyzing the chromatographic peak area in the compound band with the detector comprises: converting the compound band to a chromatogram using the detector; the chromatographic peak area in the chromatogram was calculated using the following formula:
wherein S represents the chromatographic peak area, f (t) represents the time on the abscissa and the curve function in the chromatogram of the response signal of the compound band to the detector on the ordinate, t 1 ～t 2 Representing the duration of the chromatographic peak in the chromatogram.
In an embodiment of the present invention, the calculating the disodium edentate content of the disodium edentate in the compound to be analyzed according to the chromatographic peak area includes: calculating disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area by using the following formula:
wherein Cr represents the disodium edentate content, ar represents the chromatographic peak area, cx represents the disodium edentate content of the standard control group, and Ax represents the chromatographic peak area of the standard control group.
It can be seen that, in the embodiment of the present invention, by preparing a suspension sample for adjusting the instrument parameters of the high performance liquid chromatography instrument, so as to prepare a plurality of inhalation budesonide suspensions with different concentrations, and thus, by using the inhalation budesonide suspension to output a chromatogram of disodium edetate in the plurality of inhalation budesonide suspensions with different concentrations, by reversely analyzing the chromatograms of disodium edetate, the separation effect of disodium edetate in which concentration of inhalation budesonide suspension is better, and finally selecting a suitable concentration of inhalation budesonide suspension, further, by constructing a mobile phase in the liquid storage tank, the embodiment of the present invention is used for carrying a sample to be analyzed to a chromatographic column by using the mobile phase in the subsequent step, and separating different compound components in the sample to be analyzed, according to the embodiment of the invention, the spectral peak separation degree of disodium edentate in the suspension sample is calculated based on the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump and the chromatographic column attribute of the chromatographic column, so that the spectral peak separation degree of disodium edentate under the mobile phase attribute of different sizes, the high-pressure pump attribute of different sizes and the chromatographic column attribute of different sizes is observed, when the spectral peak separation degree of disodium edentate is better, the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute which can improve the spectral peak separation degree are selected from a plurality of mobile phase attributes of different sizes, the high-pressure pump attribute and the chromatographic column attribute of different sizes, the subsequent disodium edentate content was calculated using the chromatographic peak area. Therefore, the analysis method of the content of the disodium edetate in the budesonide suspension for inhalation provided by the embodiment of the invention can improve the accuracy of measuring the content of the disodium edetate.
FIG. 4 is a functional block diagram of the disodium edentate content analysis system in the budesonide suspension for inhalation according to the present invention.
The system 400 for analyzing the disodium edetate content of the budesonide suspension for inhalation according to the present invention may be installed in an electronic device. Depending on the functions implemented, the system for analysis of disodium edetate content in a budesonide suspension for inhalation may include a material acquisition module 401, a degree of separation calculation module 402, a parameter determination module 403, a band construction module 404, and a content calculation module 405. The module of the invention, which may also be referred to as a unit, refers to a series of computer program segments, which are stored in the memory of the electronic device, capable of being executed by the processor of the electronic device and of performing a fixed function.
In the embodiment of the present invention, the functions of each module/unit are as follows:
the material acquisition module 401 is configured to acquire a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, where the high performance liquid chromatography instrument includes a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator, and a detector;
The separation degree calculation module 402 is configured to prepare a suspension sample for adjusting an instrument parameter of the high performance liquid chromatography instrument, construct a mobile phase in the liquid storage tank, and calculate a spectral peak separation degree of disodium edentate in the suspension sample based on a mobile phase attribute of the mobile phase, a high pressure pump attribute of the high pressure pump, and a chromatographic column attribute of the chromatographic column;
the parameter determining module 403 is configured to determine, based on the peak separation degree, a mobile phase parameter, a high pressure pump parameter, and a chromatographic column parameter of the high performance liquid chromatography apparatus from the mobile phase attribute, the high pressure pump attribute, and the chromatographic column attribute;
the band construction module 404 for storing the budesonide suspension for inhalation into the sample injector, and based on the high pressure pump parameters, emitting the regulated mobile phase from the reservoir into the sample injector with the high pressure pump, in the sample injector, transmitting the budesonide suspension for inhalation into the chromatographic column through the regulated mobile phase according to the mobile phase parameters, in the chromatographic column, constructing a compound band of a compound to be analyzed separated from the budesonide suspension for inhalation based on the chromatographic column parameters and the regulated mobile phase;
The content calculation module 405 is configured to analyze a chromatographic peak area in the compound band with the detector, and calculate an edetate disodium content of edetate disodium in the compound to be analyzed according to the chromatographic peak area.
In detail, the modules in the system 400 for analyzing the content of disodium edetate in the budesonide suspension for inhalation according to the embodiments of the present invention use the same technical means as the method for analyzing the content of disodium edetate in the budesonide suspension for inhalation described in fig. 1 to 3, and can produce the same technical effects, and are not described here again.
The present invention also provides a storage medium storing a computer program which, when executed by a processor of an electronic device, can implement:
the method comprises the steps of obtaining a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, wherein the high performance liquid chromatography instrument comprises a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator and a detector;
preparing a suspension sample for adjusting instrument parameters of the high performance liquid chromatography instrument, constructing a mobile phase in the liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of the high pressure pump and the chromatographic column attribute of the chromatographic column;
Determining mobile phase parameters, high-pressure pump parameters and chromatographic column parameters of the high-performance liquid chromatographic instrument from the mobile phase attributes, the high-pressure pump attributes and the chromatographic column attributes based on the spectrum peak separation degree;
storing the inhalation budesonide suspension into the sample injector, and based on the high pressure pump parameters, transmitting the regulated mobile phase from the liquid storage tank into the sample injector by the high pressure pump, in the sample injector, transmitting the inhalation budesonide suspension into the chromatographic column through the regulated mobile phase according to the mobile phase parameters, and constructing a compound band of a compound to be analyzed separated from the inhalation budesonide suspension in the chromatographic column based on the chromatographic column parameters and the regulated mobile phase;
analyzing the chromatographic peak area in the compound band by using the detector, and calculating the disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area.
In the several embodiments provided by the present invention, it should be understood that the disclosed apparatus, system and method may be implemented in other manners. For example, the system embodiments described above are merely illustrative, e.g., the division of the modules is merely a logical function division, and other manners of division may be implemented in practice.
The modules described as separate components may or may not be physically separate, and components shown as modules may or may not be physical units, may be located in one place, or may be distributed over multiple network units. Some or all of the modules may be selected according to actual needs to achieve the purpose of the solution of this embodiment.
In addition, each functional module in the embodiments of the present invention may be integrated in one processing unit, or each unit may exist alone physically, or two or more units may be integrated in one unit. The integrated units can be realized in a form of hardware or a form of hardware and a form of software functional modules.
The foregoing is only a specific embodiment of the invention to enable those skilled in the art to understand or practice the invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles defined herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, the present invention is not intended to be limited to the embodiments shown herein but is to be accorded the widest scope consistent with the principles and novel features disclosed herein.
Claims (10)
1. A method for analyzing the disodium edetate content of a budesonide suspension for inhalation, the method comprising:
the method comprises the steps of obtaining a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, wherein the high performance liquid chromatography instrument comprises a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator and a detector;
preparing a suspension sample for adjusting instrument parameters of the high performance liquid chromatography instrument, constructing a mobile phase in the liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of the high pressure pump and the chromatographic column attribute of the chromatographic column;
determining mobile phase parameters, high-pressure pump parameters and chromatographic column parameters of the high-performance liquid chromatographic instrument from the mobile phase attributes, the high-pressure pump attributes and the chromatographic column attributes based on the spectrum peak separation degree;
storing the inhalation budesonide suspension into the sample injector, and based on the high pressure pump parameters, transmitting the regulated mobile phase from the liquid storage tank into the sample injector by the high pressure pump, in the sample injector, transmitting the inhalation budesonide suspension into the chromatographic column through the regulated mobile phase according to the mobile phase parameters, and constructing a compound band of a compound to be analyzed separated from the inhalation budesonide suspension in the chromatographic column based on the chromatographic column parameters and the regulated mobile phase;
Analyzing the chromatographic peak area in the compound band by using the detector, and calculating the disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area.
2. The method of claim 1, wherein preparing a suspension sample for adjusting an instrument parameter of the high performance liquid chromatography instrument comprises:
collecting a concentration diluent and a sample to be diluted;
calculating the diluent dosage when the concentration diluent carries out gradient dilution on the sample to be diluted;
based on the dosage of the diluent, carrying out gradient dilution on the sample to be diluted by using the concentration diluent to obtain a gradient diluted sample;
inputting the gradient diluted sample into the high performance liquid chromatography instrument to output chromatographic peaks of edetate disodium in the gradient diluted sample through the high performance liquid chromatography instrument;
and when the chromatographic peak is not a preset flat peak, utilizing a corresponding gradient dilution sample in the gradient dilution samples of the chromatographic peak as the suspension sample.
3. The method of claim 2, wherein calculating the diluent amount of the concentration diluent for gradient dilution of the sample to be diluted comprises:
Calculating the diluent dosage when the concentration diluent is used for carrying out gradient dilution on the sample to be diluted by using the following formula:
wherein m is 2 Represents the diluent amount, m 1 Representing the weight of the sample to be diluted, and determining the weight of the sample to be diluted according to the size of a sample storage space of a sample injector of the high performance liquid chromatography instrument, wherein ρ 1 Representing the concentration of the sample to be diluted ρ 2 And p represents the dilution factor when the concentration diluent is used for carrying out gradient dilution on the sample to be diluted.
4. The method of claim 1, wherein said constructing a mobile phase in said reservoir comprises:
constructing a buffer solution and an organic phase in the liquid storage tank;
taking a mixed solution between the buffer solution and the organic phase as an initial mobile phase based on the volume ratio between the buffer solution and the organic phase;
and regulating the pH value of the initial mobile phase to obtain the mobile phase in the liquid storage tank.
5. The method of claim 1, wherein the calculating a spectral peak separation of disodium edentate in the suspension sample based on mobile phase properties of the mobile phase, high pressure pump properties of the high pressure pump, column properties of the column, comprises:
Dividing the range of the mobile phase attribute of the mobile phase, the high-pressure pump attribute of the high-pressure pump and the attribute value of the chromatographic column attribute of the chromatographic column to obtain a divided range attribute;
constructing a sample chromatographic peak of the suspension sample based on the split range attribute;
calculating the spectral peak separation degree in the sample chromatographic peak by using the following formula:
wherein q represents the spectral peak separation degree, x 2 Representing the sample chromatographic peak, x, of the disodium edentate in the suspension sample in the sample chromatographic peak 1 Representing a sample chromatographic peak adjacent to the sample chromatographic peak corresponding to disodium edentate, y 2 Indicating the low width of the chromatographic peak of the sample corresponding to disodium edentate, y 1 Indicating the low width of the sample chromatographic peak adjacent to the sample chromatographic peak corresponding to disodium edentate.
6. The method of claim 1, wherein determining mobile phase parameters, high pressure pump parameters, column parameters of the high performance liquid chromatography instrument from the mobile phase properties, the high pressure pump properties, the column properties based on the spectral peak separation, comprises:
extracting a maximum spectral peak separation from the spectral peak separation;
obtaining a target range attribute corresponding to the maximum spectral peak separation degree in a dividing range attribute corresponding to the mobile phase attribute, the high-pressure pump attribute and the chromatographic column attribute;
Constructing a relation model between the maximum spectrum peak separation degree and the target range attribute;
and selecting mobile phase parameters, high-pressure pump parameters and chromatographic column parameters which can enable the maximum spectral peak separation degree to reach the upper separation degree limit from the target range attribute based on the relation model.
7. The method of claim 6, wherein said constructing a model of a relationship between said maximum spectral peak separation and said target range property comprises:
constructing a relation model between the maximum spectral peak separation degree and the target range attribute by using the following formula:
wherein,representing the relation model, alpha representing the chromatographic column performance in the target range property, beta representing the compound separation performance between the mobile phase in the target range property and the stationary phase in the chromatographic column, gamma representing the capacity factor between the mobile phase in the target range property and the stationary phase in the chromatographic column, q' representing the maximum spectral peak separation.
8. The method of claim 1, wherein said analyzing chromatographic peak areas in said compound bands with said detector comprises:
converting the compound band to a chromatogram using the detector;
The chromatographic peak area in the chromatogram was calculated using the following formula:
wherein S represents the chromatographic peak area, f (t) represents the time on the abscissa and the curve function in the chromatogram of the response signal of the compound band to the detector on the ordinate, t 1 ～t 2 Representing the duration of the chromatographic peak in the chromatogram.
9. The method according to claim 1, wherein said calculating the disodium edentate content of disodium edentate in said compound to be analyzed from said chromatographic peak areas comprises:
calculating disodium edentate content of disodium edentate in the compound to be analyzed according to the chromatographic peak area by using the following formula:
wherein Cr represents the disodium edentate content, ar represents the chromatographic peak area, cx represents the disodium edentate content of the standard control group, and Ax represents the chromatographic peak area of the standard control group.
10. A system for analyzing the disodium edetate content of a budesonide suspension for inhalation, the system comprising:
the material acquisition module is used for acquiring a budesonide suspension for inhalation and a high performance liquid chromatography instrument for analyzing the content of disodium edentate in the budesonide suspension for inhalation, wherein the high performance liquid chromatography instrument comprises a liquid storage tank, a high pressure pump, a sample injector, a chromatographic column, an incubator and a detector;
The separation degree calculation module is used for preparing a suspension sample for adjusting instrument parameters of the high performance liquid chromatography instrument, constructing a mobile phase in the liquid storage tank, and calculating the spectral peak separation degree of disodium edentate in the suspension sample based on the mobile phase attribute of the mobile phase, the high pressure pump attribute of the high pressure pump and the chromatographic column attribute of the chromatographic column;
a parameter determining module, configured to determine a mobile phase parameter, a high pressure pump parameter, and a chromatographic column parameter of the high performance liquid chromatography apparatus from the mobile phase attribute, the high pressure pump attribute, and the chromatographic column attribute based on the peak separation degree;
a band build module for storing the budesonide suspension for inhalation into the sample injector and emitting the regulated mobile phase from the reservoir into the sample injector with the high pressure pump based on the high pressure pump parameter, in the sample injector, the budesonide suspension for inhalation is transported into the chromatographic column by the regulated mobile phase according to the mobile phase parameter, in the chromatographic column, a compound band of a compound to be analyzed separated from the budesonide suspension for inhalation is built based on the chromatographic column parameter and the regulated mobile phase;
And the content calculation module is used for analyzing the chromatographic peak area in the compound band by using the detector and calculating the disodium edentate content of the disodium edentate in the compound to be analyzed according to the chromatographic peak area.
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