CN114839287B - Method for detecting sodium myristate in miboplatin - Google Patents
Method for detecting sodium myristate in miboplatin Download PDFInfo
- Publication number
- CN114839287B CN114839287B CN202210447404.XA CN202210447404A CN114839287B CN 114839287 B CN114839287 B CN 114839287B CN 202210447404 A CN202210447404 A CN 202210447404A CN 114839287 B CN114839287 B CN 114839287B
- Authority
- CN
- China
- Prior art keywords
- mobile phase
- detection
- miboplatin
- sodium
- sodium tetradecanoate
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/62—Detectors specially adapted therefor
- G01N30/74—Optical detectors
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/86—Signal analysis
- G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
Landscapes
- Physics & Mathematics (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Engineering & Computer Science (AREA)
- Library & Information Science (AREA)
- Spectroscopy & Molecular Physics (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The invention relates to the technical field of medicine analysis and detection, and particularly discloses a detection method of sodium tetradecanoate in miboplatin. The detection method of the invention comprises the steps of dissolving a sample with ethanol, adding water, filtering to obtain a solution to be detected, and detecting by adopting a high performance liquid chromatography method under the following chromatographic conditions: chromatographic column: an octyl silane bonded silica gel column; an evaporative light scattering detector; mobile phase a:0.015mol/L to 0.025mol/L of ammonium acetate aqueous solution, and the mobile phase B is methanol; the elution mode is gradient elution. The detection method provided by the invention does not need derivatization treatment, has the advantages of simple and common equipment, low detection cost and high detection sensitivity, can realize the effective separation between sodium myristate and the platinum and other components, has good sodium myristate peak shape and high detection sensitivity, and is proved by methodology such as specificity, sensitivity and the like, the method provided by the invention is sensitive, accurate and better in reproducibility, and can realize the accurate quantitative detection of sodium myristate in the platinum by a simpler method.
Description
Technical Field
The invention relates to the technical field of medicine analysis and detection, in particular to a detection method of sodium tetradecanoate in miboplatin.
Background
Miliplatin (SM-11355) is a fat-soluble platinum anti-tumor drug, and is clinically used for treating hepatocellular carcinoma, and the chemical name is cis- [ (1R, 2R) -1, 2-cyclohexanediamine-N, N' ] bitetradecanoyloxy platinum monohydrate.
Sodium myristate is an important starting material for preparing the miboplatin, and the sodium myristate is doped in a finished product of the miboplatin bulk drug to directly influence the purity of the finished product of the miboplatin, so that the content of the sodium myristate in the miboplatin needs to be strictly controlled. The detection method for detecting sodium myristate in the milplatin by using the existing hydrochloric acid-methanol para-tetradecanoic acid derivatization treatment mainly has the following problems: because the miboplatin structure contains the double-tetradecanoic acid chain, the tetradecanoic acid chain can fall off and react with methanol to generate methyl myristate under an acidic condition to interfere detection, and meanwhile, the treatment method of a sample to be tested is complicated and the instrument and equipment are expensive, the method for derivatizing the tetradecanoic acid by adopting hydrochloric acid-methanol is not suitable for detecting sodium myristate in the miboplatin; the ultraviolet absorption of sodium tetradecanoate is terminal absorption, the absorption is weak, and the solubility of the miboplatin in water is poor, so if the limit is controlled to be 0.1% -0.3%, the sensitivity of the ultraviolet detector can not meet the detection requirement; anion and cation can be detected by ion chromatography, sodium myristate can ionize under alkaline condition to generate anion myristate, but the myristate has longer carbon chain and can be adsorbed in a chromatographic column, and a single alkaline eluent can not elute the myristate from the column, for example, acetonitrile is added in the eluent, and an external water mode is needed for a suppressor, so that the method is complex, the service life of the suppressor can be reduced, and the equipment cost is increased; the detection cost of the liquid chromatography-mass spectrometry combined detection method is high, and the instrument and equipment cost of a medicine production enterprise can be additionally increased, so that the method is not beneficial to energy conservation and environmental protection.
Disclosure of Invention
In view of the above, the invention provides a detection method of sodium tetradecanoate in miboplatin, which does not need derivatization treatment, has simple and common equipment, low detection cost and high detection sensitivity, and overcomes the defects of the prior art.
In order to achieve the aim of the invention, the invention adopts the following technical scheme:
the invention provides a method for detecting sodium tetradecanoate in miboplatin, which comprises the steps of dissolving a sample with ethanol, adding water, filtering to obtain a solution to be detected, detecting by adopting a high performance liquid chromatography, wherein the chromatographic conditions are as follows:
chromatographic column: an octyl silane bonded silica gel column;
a vapor light scattering detector, wherein the temperature of a drift tube is 38-42 ℃, the flow rate of carrier gas is 1.4-1.6L/min, and a shunt mode is adopted;
mobile phase a:0.015mol/L to 0.025mol/L of ammonium acetate aqueous solution, and the mobile phase B is methanol;
the elution mode is gradient elution.
According to the method for detecting sodium tetradecanoate in the miriplatin, provided by the invention, derivatization treatment is not needed, the treatment mode of a sample is simple, the miriplatin is dissolved by absolute ethyl alcohol firstly, and then most of the miriplatin is precipitated by water, so that the interference of high-concentration miriplatin is avoided, if absolute ethyl alcohol is used as a solvent, the sodium tetradecanoate is influenced by the solvent effect, abnormal peak shape can occur, and meanwhile, the risk of the interference detection of the miriplatin can be increased; according to the detection method, an octyl silane bonded silica gel column is used as a chromatographic column, an ammonium acetate aqueous solution with the concentration of 0.015mol/L to 0.025mol/L and methanol are used as mobile phases, elution is carried out in a gradient elution mode through a high performance liquid chromatography, meanwhile, detection is carried out by using an evaporative light scattering detector under the condition that the temperature of a drift tube is 38 to 42 ℃ and the flow rate of carrier gas is 1.4 to 1.6L/min, effective separation between sodium tetradecanoate and platinum and other components can be realized, and sodium tetradecanoate has good peak shape and high detection sensitivity. Through research and verification of methodology such as specificity and sensitivity, the detection method provided by the invention has the advantages of high sensitivity, good accuracy and repeatability, and capability of realizing accurate quantitative detection of sodium tetradecanoate in the miriplatin by a simple and quick method, thereby providing reliable guarantee for better monitoring the quality of the miriplatin bulk pharmaceutical chemical and having very important significance for improving the medication safety.
Preferably, the elution procedure of the gradient elution is as follows:
0min,25% mobile phase a,75% mobile phase B;
10min,2% mobile phase a,98% mobile phase B;
15min,2% mobile phase A,98% mobile phase B;
16min,25% mobile phase a,75% mobile phase B;
25min,25% mobile phase A,75% mobile phase B;
the flow rate is 0.9-1.1 ml/min.
The gradient elution sequence can improve the separation degree between sodium myristate and the milplatin in the milplatin and the sensitivity of detection, so that the detection result is accurate in quantification and high in precision.
Preferably, the flow rate is 1.0mL/min.
The preferred flow rate allows for a higher degree of separation between the sodium tetradecanoate in the miplatin and other impurities.
Preferably, the column is ZORBAX Eclipse plus C, 250X 4.6mm,5 μm.
The optimized chromatographic column specification can ensure that the peak shape, the separation degree and the detection sensitivity of each component are good, and the baseline interference is small, thereby being beneficial to the effective separation of sodium myristate from the miriplatin and other impurities in the miriplatin, and the result is accurate and reliable, and the repeatability is good.
Preferably, the column temperature is 30 to 40 ℃.
More preferably, the column temperature is 35 ℃.
The preferred detection conditions can enable the sodium myristate in the Miboplatin to achieve higher separation degree with the Miboplatin and other impurities, thereby achieving the purpose of effectively and accurately controlling the sodium myristate content in the Miboplatin.
Preferably, the sample volume is 75 to 150. Mu.L.
Preferably, mobile phase A is a 0.02mol/L aqueous ammonium acetate solution.
The preferred mobile phase A can reduce band tailing and improve peak shape, thereby being beneficial to improving the separation degree among components and leading the accuracy and precision of the detection result to be higher.
Preferably, the temperature of the drift tube is 40 ℃ and the gas flow rate is 1.5L/min.
The preferred evaporative light scattering detector adopts a shunt mode, the temperature of a drift tube is limited to be 40 ℃, the gas flow is 1.5L/min, the sodium tetradecanoate peak shape is good at the moment, the quantitative limit is 1.15ug/ml, and the sensitivity can meet the requirements.
The detection method provided by the invention does not need derivatization treatment, has the advantages of simple and common equipment, low detection cost and high detection sensitivity, can realize the effective separation between sodium myristate and the milboplatin and other components, accurately detect the content of sodium myristate in the milboplatin, is simple and quick to operate, provides a reliable method for the preparation process of the milboplatin bulk drug and the quality control of the product, and is beneficial to improving the medication safety of patients.
Drawings
FIG. 1 is a chromatogram of a blank solvent under the proprietary term in example 2;
FIG. 2 is a chromatogram of the control solution under the proprietary term of example 2;
FIG. 3 is a chromatogram of a system applicability solution under the specific term in example 2;
FIG. 4 is a chromatogram of a sample solution under the specific term in example 2;
FIG. 5 is a chromatogram of the sodium tetradecanoate localization solution in comparative example 1.
Detailed Description
The present invention will be described in further detail with reference to the following examples in order to make the objects, technical solutions and advantages of the present invention more apparent. It should be understood that the specific embodiments described herein are for purposes of illustration only and are not intended to limit the scope of the invention.
Example 1
The embodiment provides a detection method of sodium tetradecanoate in miboplatin.
Materials and methods:
instrument: high performance liquid chromatograph, evaporative light scattering detector, measuring flask, electronic balance.
Reagent: absolute ethanol, ammonium acetate, methanol and water.
Blank solvent: 75% ethanol.
1.1 preparation of solutions
Control solution: precisely weighing sodium myristate reference substance, adding absolute ethanol, performing ultrasonic treatment to dissolve, and diluting with blank solvent to obtain solution containing sodium myristate 3 μg per lml as reference substance solution.
System applicability solution: accurately weighing the impurity B, C, D, F, G, INT and sodium tetradecanoate reference substances respectively (wherein the structural formula of the impurity B is
The structural formula of the impurity C is as follows: />
The structural formula of the impurity D is as follows: />
The structural formula of the impurity F is as follows: />
The structural formula of the impurity G is as follows: />
) The mixture was dissolved in absolute ethanol and diluted with a blank solvent to prepare a system-applicable solution containing 50. Mu.g of impurity B, 50. Mu.g of impurity C, 50. Mu.g of impurity D, 50. Mu.g of impurity F, 50. Mu.g of impurity G, 50. Mu.g of impurity INT2 and 50. Mu.g of sodium tetradecanoate per 1 mL.
Localization solutions of impurity B, C, D, F, G, INT2 and sodium tetradecanoate: respectively precisely weighing appropriate amounts of impurity B, C, D, F, G, INT and sodium tetradecanoate reference substances, respectively placing into different measuring flasks, dissolving with absolute ethyl alcohol, and diluting with blank solvent to obtain solutions containing 0.5mg of impurity B, 0.5mg of impurity C, 0.5mg of impurity D, 0.5mg of impurity F, 0.5mg of impurity G, 0.5mg of impurity INT2 and 0.5mg of sodium tetradecanoate per 1mL, thereby obtaining respective positioning solutions.
Test solution: accurately weighing about 15mg of the sample, placing in a 10ml measuring flask, adding 7.5ml of absolute ethanol, performing ultrasonic treatment to dissolve, adding water to dilute to scale, shaking, filtering, and taking filtrate as sample solution.
1.2 conditions for high Performance liquid chromatography:
chromatographic column: ZORBAX Eclipse plus C8 (250×4.6mm,5 μm); flow rate: 1.0mL/min; column temperature, 35 ℃; sample injection amount: 100. Mu.L; mobile phase a phase: 0.02mol/L ammonium acetate aqueous solution, mobile phase B phase: methanol;
elution was performed according to the following gradient procedure:
| time (min) | Mobile phase a (%) | Mobile phase B (%) |
| 0 | 25 | 75 |
| 10 | 2 | 98 |
| 15 | 2 | 98 |
| 16 | 25 | 75 |
| 25 | 25 | 75 |
Conditions for evaporative light scattering detector: the temperature of the drift tube is 40 ℃, the flow rate of carrier gas is 1.5L/min, and the flow distribution mode is adopted.
Example 2
This example provides methodological verification of the method for detection of sodium tetradecanoate in miboplatin of example 1:
2.1 specificity
Taking a blank solvent, a reference substance solution, a sample solution, a positioning solution of impurities B, C, D, F, G, INT and sodium tetradecanoate and a system applicability solution of the embodiment 1, carrying out sample injection detection according to the detection conditions of sodium tetradecanoate in the miplatinum provided by the embodiment 1, wherein the sample injection amount is 100 mu L, recording a chromatogram, wherein the chromatographic peak of the blank solvent is shown in fig. 1, the chromatographic peak of the reference substance solution is shown in fig. 2, the chromatographic peak of the system applicability solution is shown in fig. 3, the chromatographic peak of the sample solution is shown in fig. 4, and the test results of the positioning solution of impurities B, C, D, F, G, INT2 and sodium tetradecanoate and the system applicability solution are shown in table 1:
TABLE 1
The test result shows that the baseline is stable and has no interference, and the blank solvent has no interference on the detection of impurities and main components; the separation degree between each component and each impurity is larger than 1.5, and impurity B, C, D, F, G, INT is colorless at the position of sodium tetradecanoate peak, does not interfere with sodium tetradecanoate determination, and shows that the method has good specificity.
2.2 Linear Range
Precisely weighing sodium tetradecanoate reference substance about 7.5mg, placing into a 10ml measuring flask, adding absolute ethyl alcohol, carrying out ultrasonic treatment to dissolve, diluting to a scale, shaking uniformly, precisely weighing 1.0ml, placing into a 50ml measuring flask, adding absolute ethyl alcohol to dilute to the scale, shaking uniformly, taking as a linear stock solution, precisely weighing 1.0ml, 2.0ml, 3.0ml, 4.0ml and 6.0ml of the linear stock solution, respectively placing into 10ml measuring flask, adding water 2.5ml, and diluting to the scale with absolute ethyl alcohol to obtain a linear 1/2/3/4/5 solution. Sample injection detection is carried out according to the detection conditions of sodium tetradecanoate in the miboplatin provided in example 1, the sample injection amount is 100 mu L, the peak area logarithmic value is taken as an ordinate, the concentration logarithmic value is taken as an abscissa, and the result is shown in Table 2.
TABLE 2
The above results show that sodium myristate concentration logarithmic value and peak area logarithmic value have good linear relation in the range of 1.4430-8.6581 mug/ml, linear equation y=1.9036x+8.3211, and correlation coefficient r=0.999.
2.3 quantitative limit and detection limit
Taking the linear solution prepared under the 2.2 items, respectively measuring the quantitative limit and the detection limit by a dilution method, taking the concentration at a signal-to-noise ratio of 3:1 as the detection limit, taking the concentration at a signal-to-noise ratio of 10:1 as the quantitative limit, continuously sampling the quantitative limit solution for 6 times, calculating the relative standard deviation of peak area and the relative standard deviation of retention time, wherein the quantitative limit result is shown in Table 3, and the detection limit result is shown in Table 4
TABLE 3 quantitative limit test results
TABLE 4 detection limit test results
The test result shows that the quantitative limit concentration of sodium myristate is 1.150 mug/ml, which is equivalent to 0.077% of the concentration of the main component, and the method sensitivity meets the detection requirement; the quantitative limit was repeatedly formulated 6 times, the S/N was more than 10, the retention time was 0.2% of RSD, the peak area was 5.9% of RSD, and the quantitative limit was good in reproducibility. The detection limit concentration of sodium tetradecanoate is 0.575 mug/ml, which is equivalent to 0.038% of the concentration of the main component, and the S/N is more than 3, which shows that the method has high sensitivity.
2.4 repeatability
6 parts of sample solution are taken, sample injection detection is carried out according to the detection condition of sodium tetradecanoate in the miboplatin provided in the example 1, the sample injection amount is 100 mu L, a chromatogram is recorded, and the content of sodium tetradecanoate is calculated, and the result is shown in Table 5.
TABLE 5 repeatability test results
The test result shows that the detection results of 6 parts of test sample solutions have no obvious difference, the average value of sodium tetradecanoate content is 0.14%, and rsd=6.8%, so that the method has good repeatability.
2.5 accuracy
Precisely weighing about 15mg of a sample, placing the sample into a 10ml measuring flask, respectively adding 1.0ml, 2.0ml and 3.0ml of linear stock solution prepared under 2.2 items, respectively adding 6.5ml, 5.5ml and 4.5ml of absolute ethyl alcohol, ultrasonically dissolving, placing the sample to room temperature, diluting to a scale with water, filtering the sample by using a Polytetrafluoroethylene (PTFE) filter membrane, and obtaining filtrate to obtain low-recovery, medium-recovery and high-recovery solutions, wherein 3 parts of each solution is prepared in parallel.
100. Mu.l of each of the above solutions was measured precisely, injected into a liquid chromatograph, subjected to sample injection detection under the detection conditions of sodium tetradecanoate in the miplatin provided in example 1, and the chromatograms were recorded, and the recovery rate of each impurity and the RSD value of the recovery rate were calculated, with the results shown in Table 6 below.
TABLE 6 accuracy test results
The results show that the recovery rate of 9 parts of the test sample is 93.2% -103.1%, the average recovery rate is 99.5%, and the RSD is 5.5%, so that the method has good accuracy and meets the sodium tetradecanoate measurement requirement.
2.6 durability
The influence of the micro-adjustment of the chromatographic conditions on the sensitivity and specificity of the method was examined by adjusting factors such as different flow rates, column temperatures, mobile phase buffer salt concentrations, mobile phase proportions, different batches of chromatographic columns, the temperature of the drift tube of the evaporative light scattering detector, and gas flow rate on the basis of the chromatographic conditions of example 1, and the results are shown in Table 7.
TABLE 7 durability test results
The results show that the chromatographic conditions are slightly adjusted, the sensitivity and the specificity of the method are good, and the method is proved to have good durability of the chromatographic conditions.
2.7 intermediate precision
6 parts of sample solution are taken, different analysts respectively adopt chromatographic columns of different batches and instruments of the same model and different batches at different times, sample injection detection is carried out according to the detection conditions of sodium tetradecanoate in the miboplatin provided in the example 1, the sample injection amount is 100 mu L, the chromatogram is recorded, and the test results are shown in Table 8.
TABLE 8
TABLE 9
The results show that different analysts respectively measure the same batch of samples at different times by adopting chromatographic columns of different batches and instruments of the same model and different batches, the average content of sodium tetradecanoate in 12 samples to be tested is 0.16%, and the RSD is 12.1%, which indicates that the method has good intermediate precision.
2.8 solution stability
Taking the linear 2 solution prepared under the 2.2 item and the sample solution to be tested, respectively placing the solutions at room temperature for different times, and carrying out sample injection detection according to the detection conditions of sodium tetradecanoate in the miboplatin provided in the example 1, wherein the sample injection amount is 100 mu L, and the solution stability results are shown in Table 10.
TABLE 10 stability results of test solutions
| MB-211015B | 0h | 2h | 4h | 6h |
| A | 21497 | 24388 | 34578 | 45022 |
| ln(A) | 9.976 | 10.102 | 10.451 | 10.715 |
| Recovery% | N/A | 101.3 | 104.8 | 107.4 |
TABLE 11 stability results of control solutions
| Linearity 2 | 0h | 10.5h | 14h | Average of | RSD％ |
| A | 29008 | 34699 | 35659 | 33122 | -- |
| ln(A) | 10.275 | 10.454 | 10.482 | 10.404 | 1.1 |
The results show that the recovery rate of the peak area logarithmic value relative to 0 time is 98-102% when the sample solution is placed for 2 hours at room temperature, and the sample solution is stable within 2 hours at room temperature; the control solution was left at room temperature for 14 hours, the RSD of the peak area log value was 1.1%, and the control solution was stable at room temperature for 14 hours.
Comparative example 1
The comparative example provides a method for detecting sodium tetradecanoate in miboplatin tested in the research process, and the detection analysis is carried out according to the following chromatographic conditions:
conditions of high performance liquid chromatography:
chromatographic column: ZORBAX Eclipse plus C8 (250×4.6mm,5 μm); flow rate: 1.0mL/min; column temperature, 35 ℃; sample injection amount: 25 μL; mobile phase a phase: water, mobile phase B phase: methanol;
elution was performed according to the following gradient procedure:
| time (min) | Mobile phase a (%) | Mobile phase B (%) |
| 0 | 25 | 75 |
| 10 | 2 | 98 |
| 15 | 2 | 98 |
| 16 | 25 | 75 |
| 25 | 25 | 75 |
Conditions for evaporative light scattering detector: the temperature of the drift tube is 80 ℃, the flow rate of carrier gas is 2.0L/min, and the flow rate of the carrier gas is Impactor: off (no shunt mode).
Preparing sodium tetradecanoate positioning solution: weighing sodium myristate as reference, precisely weighing, adding ethanol, dissolving with ultrasound, and diluting with 75% ethanol to obtain solution containing sodium myristate 1.0 mg/lml. Taking sodium tetradecanoate positioning solution, carrying out sample injection detection according to the conditions of the high performance liquid chromatography, and recording a chromatogram, wherein the chromatogram of the sodium tetradecanoate positioning solution is shown in fig. 5, and as can be seen from fig. 5, the sodium tetradecanoate positioning solution has poor peak shape, serious tailing, low theoretical plate number and low sensitivity, and cannot meet the requirement of sensitivity.
Comparative example 2
The comparative example provides a method for detecting sodium tetradecanoate in miboplatin tested in the research process, and the detection analysis is carried out according to the following chromatographic conditions:
conditions of high performance liquid chromatography:
chromatographic column: ZORBAX Eclipse plus C8 (250×4.6mm,5 μm); flow rate: 1.0mL/min; column temperature, 35 ℃; sample injection amount: 100. Mu.L; mobile phase a phase: 0.02mol/L ammonium acetate aqueous solution, mobile phase B phase: methanol;
elution was performed according to the following gradient procedure:
| time (min) | Mobile phase a (%) | Mobile phase B (%) |
| 0 | 25 | 75 |
| 10 | 2 | 98 |
| 15 | 2 | 98 |
| 16 | 25 | 75 |
| 25 | 25 | 75 |
Conditions for evaporative light scattering detector: the temperature of the drift tube is 115 ℃, the flow rate of carrier gas is 3.0L/min, and the flow rate of the carrier gas is Impactor: off (no shunt mode).
Preparing sodium tetradecanoate positioning solution: weighing sodium myristate as reference, precisely weighing, adding ethanol, dissolving with ultrasound, and diluting with 75% ethanol to obtain solution containing sodium myristate 0.5 mg/lml. And taking a blank solvent and sodium myristate positioning solution, and carrying out sample injection detection according to the conditions of the high performance liquid chromatography, wherein a chromatographic peak of sodium myristate cannot be detected in the sodium myristate positioning solution, so that the requirement of sensitivity cannot be met.
Comparative example 3
The comparative example provides a method for detecting sodium tetradecanoate in miboplatin tested in the research process, and the detection analysis is carried out according to the following chromatographic conditions:
conditions of high performance liquid chromatography:
chromatographic column: CAPCELL PAK AQ-C18 (250X 4.6mm,5 μm); flow rate: 1.0mL/min; column temperature, 35 ℃; sample injection amount: 100. Mu.L; mobile phase a phase: 0.02mol/L ammonium acetate aqueous solution, mobile phase B phase: methanol;
elution was performed according to the following gradient procedure:
conditions for evaporative light scattering detector: the temperature of the drift tube is 115 ℃, the flow rate of carrier gas is 3.0L/min, and the flow rate of the carrier gas is Impactor: off (no shunt mode).
Preparing sodium tetradecanoate positioning solution: weighing sodium myristate as reference, precisely weighing, adding ethanol, dissolving with ultrasound, and diluting with 75% ethanol to obtain solution containing sodium myristate 0.5 mg/lml. And taking a blank solvent and sodium myristate positioning solution, and carrying out sample injection detection according to the conditions of the high performance liquid chromatography, wherein a chromatographic peak of sodium myristate cannot be detected in the sodium myristate positioning solution, so that the requirement of sensitivity cannot be met.
The foregoing description of the preferred embodiments of the invention is not intended to be limiting, but rather is intended to cover all modifications, equivalents, or alternatives falling within the spirit and principles of the invention.
Claims (8)
1. A detection method of sodium tetradecanoate in miboplatin is characterized in that a sample is dissolved by ethanol, water is added and filtered to obtain a solution to be detected, and high performance liquid chromatography is adopted for detection, wherein the chromatographic conditions are as follows:
chromatographic column: an octyl silane bonded silica gel column;
a vapor light scattering detector, wherein the temperature of a drift tube is 38-42 ℃, the flow rate of carrier gas is 1.4-1.6L/min, and a shunt mode is adopted;
mobile phase a:0.015mol/L to 0.025mol/L of ammonium acetate aqueous solution, and the mobile phase B is methanol;
the elution mode is gradient elution, and the elution procedure is as follows:
0min,25% mobile phase a,75% mobile phase B;
10min,2% mobile phase a,98% mobile phase B;
15min,2% mobile phase A,98% mobile phase B;
16min,25% mobile phase a,75% mobile phase B;
25min,25% mobile phase A,75% mobile phase B;
the flow rate is 0.9-1.1 ml/min.
2. The method for detecting sodium tetradecanoate in miplatin according to claim 1, wherein the flow rate is 1.0mL/min.
3. The method for detecting sodium tetradecanoate in miboplatin according to claim 1, wherein the chromatographic column is ZORBAX Eclipse plus C, 250×4.6mm,5 μm.
4. The method for detecting sodium tetradecanoate in miboplatin according to claim 1, wherein the column temperature is 30-40 ℃.
5. The method for detecting sodium tetradecanoate in miplatin as claimed in claim 4, wherein the column temperature is 35 ℃.
6. The method for detecting sodium tetradecanoate in miboplatin according to claim 1, wherein the sample injection volume is 75-150 μl.
7. The method for detecting sodium tetradecanoate in miplatin according to claim 1, wherein mobile phase a is 0.02mol/L ammonium acetate aqueous solution.
8. The method for detecting sodium tetradecanoate in miplatin according to claim 1, wherein the temperature of the drift tube is 40 ℃ and the gas flow rate is 1.5L/min.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210447404.XA CN114839287B (en) | 2022-04-26 | 2022-04-26 | Method for detecting sodium myristate in miboplatin |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210447404.XA CN114839287B (en) | 2022-04-26 | 2022-04-26 | Method for detecting sodium myristate in miboplatin |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114839287A CN114839287A (en) | 2022-08-02 |
| CN114839287B true CN114839287B (en) | 2023-06-09 |
Family
ID=82565127
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210447404.XA Active CN114839287B (en) | 2022-04-26 | 2022-04-26 | Method for detecting sodium myristate in miboplatin |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114839287B (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115327022B (en) * | 2022-09-13 | 2023-10-24 | 安徽皖维高新材料股份有限公司 | Method for detecting potassium acetate content in PVB resin by adopting ion chromatography |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102127119B (en) * | 2011-01-11 | 2012-03-14 | 济南利民制药有限责任公司 | Preparation method of miboplatin |
| CN102225954B (en) * | 2011-05-05 | 2013-07-31 | 昆明贵研药业有限公司 | Method for purifying platinum |
| CN102516311B (en) * | 2011-11-03 | 2014-05-28 | 南京优科生物医药有限公司 | Preparation method of miriplatin hydrate |
| CN102879512B (en) * | 2012-09-29 | 2015-06-17 | 云南烟草科学研究院 | Method for detecting higher aliphatic acid in coffee |
| CN104597157B (en) * | 2015-01-17 | 2016-02-24 | 神威药业集团有限公司 | The assay method of a kind of liposoluble platinum complex and preparation related substance thereof |
| CN112630365B (en) * | 2020-11-27 | 2022-08-23 | 江苏东南纳米材料有限公司 | Method for determining content of dimyristoyl phosphatidylcholine by high performance liquid chromatography |
-
2022
- 2022-04-26 CN CN202210447404.XA patent/CN114839287B/en active Active
Also Published As
| Publication number | Publication date |
|---|---|
| CN114839287A (en) | 2022-08-02 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN115166080B (en) | Method for detecting impurity A and impurity B in ifosfamide bulk drug | |
| CN115097023B (en) | High performance liquid chromatography detection method for zomib amine related substances | |
| CN114839287B (en) | Method for detecting sodium myristate in miboplatin | |
| CN113295805B (en) | Method for detecting hydrazine hydrate in medicine | |
| CN111122736B (en) | Method for detecting enantiomer in intermediate of brivaracetam | |
| CN106525994B (en) | Method for determining related substances of paracetamol and tramadol capsule | |
| CN112630365A (en) | Method for determining content of dimyristoyl phosphatidylcholine by high performance liquid chromatography | |
| CN111505159A (en) | Detection method of related substances in arotinolol hydrochloride | |
| CN112611813B (en) | Method for testing genotoxic impurities of Sacubitril valsartan sodium starting material | |
| CN112763622B (en) | Method for determining plamavir through liquid chromatography | |
| CN112213418B (en) | Method for detecting related substances in sofosbuvir | |
| CN114076802A (en) | Analysis method for quantitatively detecting nitrogen and oxygen impurities in pitavastatin calcium | |
| CN107976489B (en) | Method for determining residual pyridine in pregabalin | |
| CN115480020B (en) | Method for measuring substance related to prionamine | |
| CN116183772B (en) | Method for detecting mutation-causing impurities in bulk drug | |
| CN114200050B (en) | HPLC detection method for content of related substances in p-bromoanisole | |
| CN116879428B (en) | High performance liquid analysis method for residual content of phosphorylcholine in L-alpha-phosphorylcholine | |
| CN112394112B (en) | Method for detecting content of hydroxychloroquine oxynitride impurities in hydroxychloroquine sulfate | |
| CN114965770B (en) | Method for detecting starting material, impurity D and impurity F in ifosfamide bulk drug | |
| CN117630202B (en) | Method for detecting buspirone hydrochloride intermediate impurities | |
| CN117554549A (en) | Method for simultaneously detecting dyclonine hydrochloride residual formic acid and acetic acid | |
| CN115980217A (en) | Furosemide and control method for determining content of degradation impurities in injection of furosemide | |
| CN116359371A (en) | Method for measuring urea content by high performance liquid chromatography | |
| CN114200067A (en) | High performance liquid chromatography analysis method for 6-bromo-3-hydroxypyrazine-2-formamide and impurities | |
| CN112394110A (en) | Method for detecting content of hydroxychloroquine sulfate ester impurities in hydroxychloroquine sulfate |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| GR01 | Patent grant | ||
| GR01 | Patent grant |