CN114088821A - Method for detecting domiphen bromide content in disinfection product - Google Patents
Method for detecting domiphen bromide content in disinfection product Download PDFInfo
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- CN114088821A CN114088821A CN202110985353.1A CN202110985353A CN114088821A CN 114088821 A CN114088821 A CN 114088821A CN 202110985353 A CN202110985353 A CN 202110985353A CN 114088821 A CN114088821 A CN 114088821A
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- domiphen bromide
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- dihydrogen phosphate
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- 229960001859 domiphen bromide Drugs 0.000 title claims abstract description 137
- 238000000034 method Methods 0.000 title claims abstract description 45
- 238000004659 sterilization and disinfection Methods 0.000 title claims abstract description 41
- OJIYIVCMRYCWSE-UHFFFAOYSA-M Domiphen bromide Chemical compound [Br-].CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 OJIYIVCMRYCWSE-UHFFFAOYSA-M 0.000 title claims abstract 24
- 238000001514 detection method Methods 0.000 claims abstract description 105
- WEVYAHXRMPXWCK-UHFFFAOYSA-N acetonitrile Substances CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims abstract description 83
- 239000000243 solution Substances 0.000 claims abstract description 63
- 239000007788 liquid Substances 0.000 claims abstract description 26
- 239000002904 solvent Substances 0.000 claims abstract description 23
- NBIIXXVUZAFLBC-UHFFFAOYSA-M dihydrogenphosphate Chemical compound OP(O)([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-M 0.000 claims abstract description 18
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 claims abstract description 13
- 239000000741 silica gel Substances 0.000 claims abstract description 13
- 229910002027 silica gel Inorganic materials 0.000 claims abstract description 13
- BLRPTPMANUNPDV-UHFFFAOYSA-N Silane Chemical group [SiH4] BLRPTPMANUNPDV-UHFFFAOYSA-N 0.000 claims abstract description 11
- 229910000077 silane Inorganic materials 0.000 claims abstract description 11
- 238000002347 injection Methods 0.000 claims abstract description 8
- 239000007924 injection Substances 0.000 claims abstract description 8
- 239000000645 desinfectant Substances 0.000 claims abstract description 4
- 238000005070 sampling Methods 0.000 claims abstract description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 66
- 229960000629 domiphen Drugs 0.000 claims description 26
- YXUPZGKORWTXID-UHFFFAOYSA-N domiphen Chemical compound CCCCCCCCCCCC[N+](C)(C)CCOC1=CC=CC=C1 YXUPZGKORWTXID-UHFFFAOYSA-N 0.000 claims description 26
- 229910000402 monopotassium phosphate Inorganic materials 0.000 claims description 23
- 235000019796 monopotassium phosphate Nutrition 0.000 claims description 23
- PJNZPQUBCPKICU-UHFFFAOYSA-N phosphoric acid;potassium Chemical compound [K].OP(O)(O)=O PJNZPQUBCPKICU-UHFFFAOYSA-N 0.000 claims description 22
- 239000000523 sample Substances 0.000 claims description 22
- 238000009210 therapy by ultrasound Methods 0.000 claims description 13
- 239000012488 sample solution Substances 0.000 claims description 11
- 239000012086 standard solution Substances 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 7
- 238000001914 filtration Methods 0.000 claims description 7
- 239000012528 membrane Substances 0.000 claims description 6
- 229910000403 monosodium phosphate Inorganic materials 0.000 claims description 5
- 235000019799 monosodium phosphate Nutrition 0.000 claims description 5
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 claims description 5
- 238000007865 diluting Methods 0.000 claims description 4
- 238000002203 pretreatment Methods 0.000 claims description 2
- 238000000527 sonication Methods 0.000 claims description 2
- 230000005526 G1 to G0 transition Effects 0.000 abstract description 2
- BHQQXAOBIZQEGI-UHFFFAOYSA-N methyl 2-chlorobutanoate Chemical compound CCC(Cl)C(=O)OC BHQQXAOBIZQEGI-UHFFFAOYSA-N 0.000 description 113
- 239000012071 phase Substances 0.000 description 40
- 239000000047 product Substances 0.000 description 27
- 230000000052 comparative effect Effects 0.000 description 26
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- 230000014759 maintenance of location Effects 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 238000002604 ultrasonography Methods 0.000 description 6
- 238000005303 weighing Methods 0.000 description 6
- 238000012360 testing method Methods 0.000 description 5
- 230000000694 effects Effects 0.000 description 4
- 239000000499 gel Substances 0.000 description 4
- 239000007921 spray Substances 0.000 description 4
- 238000004140 cleaning Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000006187 pill Substances 0.000 description 3
- 201000004647 tinea pedis Diseases 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000003385 bacteriostatic effect Effects 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000000249 desinfective effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000006210 lotion Substances 0.000 description 2
- 210000000214 mouth Anatomy 0.000 description 2
- 230000002035 prolonged effect Effects 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 230000001954 sterilising effect Effects 0.000 description 2
- 239000012085 test solution Substances 0.000 description 2
- PBLNBZIONSLZBU-UHFFFAOYSA-N 1-bromododecane Chemical compound CCCCCCCCCCCCBr PBLNBZIONSLZBU-UHFFFAOYSA-N 0.000 description 1
- 206010061218 Inflammation Diseases 0.000 description 1
- 201000007100 Pharyngitis Diseases 0.000 description 1
- RSAVQRSLZFCKES-UHFFFAOYSA-M S(=O)(=O)(OCCCCCCCCCCCC)[O-].[Na+].C(C)#N.CO Chemical compound S(=O)(=O)(OCCCCCCCCCCCC)[O-].[Na+].C(C)#N.CO RSAVQRSLZFCKES-UHFFFAOYSA-M 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- 206010048038 Wound infection Diseases 0.000 description 1
- 238000009098 adjuvant therapy Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 238000004364 calculation method Methods 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000002349 favourable effect Effects 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 239000008187 granular material Substances 0.000 description 1
- 230000004054 inflammatory process Effects 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- RUHVDRGWCIAFLG-UHFFFAOYSA-N n,n-dimethyl-2-phenoxyethanamine Chemical compound CN(C)CCOC1=CC=CC=C1 RUHVDRGWCIAFLG-UHFFFAOYSA-N 0.000 description 1
- 238000011056 performance test Methods 0.000 description 1
- GNSKLFRGEWLPPA-UHFFFAOYSA-M potassium dihydrogen phosphate Chemical compound [K+].OP(O)([O-])=O GNSKLFRGEWLPPA-UHFFFAOYSA-M 0.000 description 1
- LWIHDJKSTIGBAC-UHFFFAOYSA-K potassium phosphate Substances [K+].[K+].[K+].[O-]P([O-])([O-])=O LWIHDJKSTIGBAC-UHFFFAOYSA-K 0.000 description 1
- NHOXRBDMOTVJBL-UHFFFAOYSA-M potassium;dihydrogen phosphate;methanol Chemical compound [K+].OC.OP(O)([O-])=O NHOXRBDMOTVJBL-UHFFFAOYSA-M 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000002994 raw material Substances 0.000 description 1
- 239000013558 reference substance Substances 0.000 description 1
- 230000036559 skin health Effects 0.000 description 1
- 206010040872 skin infection Diseases 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 230000001502 supplementing effect Effects 0.000 description 1
- -1 therefore Natural products 0.000 description 1
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- 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
- G01N30/04—Preparation or injection of sample to be analysed
- G01N30/06—Preparation
- G01N30/14—Preparation by elimination of some components
-
- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/30—Control of physical parameters of the fluid carrier of temperature
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- 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
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
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- 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
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- 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
- G01N30/8624—Detection of slopes or peaks; baseline correction
- G01N30/8631—Peaks
- G01N30/8634—Peak quality criteria
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- 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
- G01N30/14—Preparation by elimination of some components
- G01N2030/146—Preparation by elimination of some components using membranes
Abstract
The application relates to the field of detection of disinfection products, and particularly discloses a method for detecting domiphen bromide content in the disinfection products. The method for detecting the content of domiphen bromide in the disinfection product comprises the following steps of S1: pretreating a domiphen bromide disinfection product: dissolving the domiphen bromide disinfectant with a solvent to obtain a domiphen bromide solution; s2: high performance liquid detection: sampling 10 mu L, and carrying out sample injection detection, wherein the chromatographic column adopts a C18 silane bonded silica gel column, the mobile phase adopts dihydrogen phosphate solution-acetonitrile, and the volume ratio of the dihydrogen phosphate solution to the acetonitrile is (20-30): (70-85), the pH value of the mobile phase is 2-3, and the detection wavelength is 265-275 nm. The application provides a detection method of domiphen bromide in pharmacopeia, which is completely different from a mobile phase and a stationary phase in the pharmacopeia, and has the advantages of low cost, large detection range, small relative standard deviation and low detection limit compared with the domiphen bromide in the pharmacopeia.
Description
Technical Field
The application relates to the field of detection of disinfection products, in particular to a method for detecting domiphen bromide content in the disinfection products.
Background
Domiphen bromide is white or yellowish crystal, is very soluble in ethanol and chloroform, is soluble in water, but is almost insoluble in ether, is prepared from bromododecane and phenoxyethyl dimethylamine, is commonly used as a bactericide and a disinfectant, and can be used for the adjuvant treatment of oral cavity and throat infection and the disinfection of skin and wound infection and surgical instruments.
A method for measuring domiphen bromide under the item of Chinese pharmacopoeia domiphen bromide dropping pills, the domiphen bromide dropping pills: the product contains domiphen bromide (C)22H40BrNO·H2O) should be 85.0% to 115.0% of the indicated amount; content determination: measuring by high performance liquid chromatography (general rule 0512), a, collecting 20 granules of the product, precisely weighing, dissolving with mobile phase, quantitatively diluting to obtain solution containing domiphen 0.8mg per 1ml, and filtering if necessary; b. taking a proper amount of domiphen bromide as a reference substance solution, precisely weighing, adding a mobile phase for dissolving, and quantitatively diluting to prepare a solution containing 0.8mg in each 1 ml; c. chromatographic conditions, sulfonated cross-linked styrene-divinyl copolymer is used as a filler, and methanol-0.05 mol/L sodium acetate solution (80: 20) is used as a mobile phase; the detection wavelength was 274nm and the sample volume was 10. mu.L.
In view of the above-mentioned related technologies, the inventor considers that the above-mentioned method is not suitable for directly applying to the detection of domiphen content in the disinfection product, and has the defect of inaccurate detection result.
Disclosure of Invention
In order to solve the problem that the detection result is inaccurate when the method is directly used for detecting the content of the domiphen in the disinfection product, the application provides the method for detecting the content of the domiphen in the disinfection product.
The application provides a method for detecting the content of domiphen bromide in a disinfection product, which comprises the following steps:
s1: pretreating a domiphen bromide disinfection product: dissolving the domiphen bromide disinfectant with a solvent to obtain a domiphen bromide solution;
s2: high performance liquid detection: sampling 10 mu L, and carrying out sample injection detection, wherein the chromatographic column adopts a C18 silane bonded silica gel column, the mobile phase adopts dihydrogen phosphate solution-acetonitrile, and the volume ratio of the dihydrogen phosphate solution to the acetonitrile is (20-30): (70-85), the pH value of the mobile phase is 2-3, and the detection wavelength is 265-275 nm.
By adopting the technical scheme, the C18 silane bonded silica gel column is a universal high performance liquid chromatography column and is low in price, and the sulfonated cross-linked styrene-divinyl copolymer chromatography column used in pharmacopoeia is high in price and single in applicability. The mobile phase in the method adopts the dihydrogen phosphate solution and the acetonitrile, namely, the method provides a mobile phase completely different from that in pharmacopoeia, and the ratio of the dihydrogen phosphate solution to the acetonitrile is adjusted; compared with the detection method of the content of the domiphen bromide in the pharmacopoeia, the method uses the specific chromatographic column and the flow of a specific proportion to be matched for use, when the content of the domiphen bromide in the disinfection product is detected, the detection linear range of the detection method is larger, and the relative standard deviation is smaller, so that the detection result is more accurate, and the detection limit is lower.
Optionally, the volume ratio of the dihydrogen phosphate solution to the acetonitrile in the step S2 is (23-25): (75-77).
By adopting the technical scheme, the proportion of the dihydrogen phosphate solution to the acetonitrile is further adjusted, so that a polar part and a non-polar part in the domiphen sterilizing article which is driven by the mobile phase to enter the chromatographic column are well separated, the detected peak area is closer to the standard peak area of the domiphen, and the standard deviation of multiple experiments is smaller, so that the detection limit for finally detecting the domiphen content in the sterilizing article is lower.
Alternatively, in S1, the solvent is methanol.
By adopting the technical scheme, because the domiphen bromide can be dissolved in water and is easy to dissolve in ethanol, and the polarity of methanol is greater than that of ethanol, the solubility of the domiphen bromide in the methanol is stronger, and when the domiphen bromide is dissolved by two solvents of methanol and ethanol respectively, the methanol is used as the solvent to dissolve the domiphen bromide more completely, so that the detection limit of the domiphen bromide dissolved by the methanol as the solvent is lower when the domiphen bromide is detected.
Optionally, the S1 further includes a step of subjecting the domiphen bromide dissolving solution to ultrasonic treatment for 10-30min to obtain a domiphen bromide pretreatment solution.
By adopting the technical scheme, the ultrasonic treatment of the domiphen bromide solution aims at better dissolving the domiphen bromide in methanol, so that the separation effect of the domiphen bromide in a polar mobile phase and a non-polar chromatographic column is better, the detected peak shape is closer to the standard peak shape, and the detection limit of the domiphen bromide is finally measured to be lower.
Optionally, the S1 further includes a step of cooling the domiphen bromide pretreatment solution to room temperature, and re-diluting the domiphen bromide pretreatment solution to a volume before sonication by using the solvent in S1 to obtain the domiphen bromide standard solution.
By adopting the technical scheme, the ultrasonic operation can cause the temperature of the domiphen bromide pretreatment liquid to be subjected to ultrasonic treatment to rise, so that the volume of the domiphen bromide pretreatment liquid is reduced due to evaporation at high temperature, and the measured volume is not the standard volume at normal temperature, thereby influencing the later detection accuracy; therefore, the domiphen bromide pretreatment liquid needs to be cooled to room temperature, then the volume is fixed to the volume before ultrasonic treatment, the solvent lost in the ultrasonic process is supplemented, finally, the concentration of the domiphen bromide dissolved by the solvent is closer to the initial concentration of the domiphen bromide pretreatment liquid, and further, the detection limit obtained through the detection result is more accurate. And when the instrument precision experiment is carried out, the domiphen bromide concentration detected every time has no larger deviation and has smaller standard deviation.
Optionally, the ultrasonic treatment is ice bath ultrasonic, and the ultrasonic temperature is 0-10 ℃.
Through adopting above-mentioned technical scheme, when carrying out the supersound, along with the extension of supersound time, the temperature can rise gradually, then the solvent is volatile faster, and the solvent volatilizees the concentration that can influence the domiphen pretreatment liquid too fast, finally influences the testing result, consequently carries out ice bath supersound, and low temperature when maintaining the supersound is favorable to guaranteeing the accuracy of domiphen pretreatment liquid concentration to guarantee the accuracy and the reliability of testing result.
Optionally, the S1 further includes a step of filtering the domiphen bromide solution, the domiphen bromide pretreatment solution or the domiphen bromide standard solution with a filter membrane smaller than or equal to 0.45 μm to obtain the domiphen bromide sample solution.
By adopting the technical scheme, the domiphen bromide standard solution is filtered by the filter membrane, and impurities in the domiphen bromide standard solution are filtered, so that the finally detected domiphen bromide solution has less impurity content, the peak area of the high performance liquid chromatography peak only contains the peak area of the domiphen bromide, the peak area of the domiphen bromide cannot be influenced by other impurities, and the linear relation is more standard.
Optionally, the pH of the mobile phase in the step S2 is 2.3-2.5.
By adopting the technical scheme, due to the polar group contained in the domiphen bromide, for the compound containing the polar functional group, the pH can influence the existing state of the compound, and further influence the separation selectivity and the symmetry of a chromatographic peak; by further adjusting the pH value of the dihydrogen phosphate mobile phase, the domiphen bromide can be better separated in the mobile phase with a proper pH value, and the detection limit of the domiphen bromide is favorably reduced.
Optionally, the dihydrogen phosphate solution is one of sodium dihydrogen phosphate and potassium dihydrogen phosphate.
By adopting the technical scheme, the sodium dihydrogen phosphate or the potassium dihydrogen phosphate are two commonly used pH buffer solutions, the potassium dihydrogen phosphate or the sodium dihydrogen phosphate and acetonitrile respectively form a mobile phase according to a certain volume ratio, the domiphen detection in the disinfection product is carried out, and the detection result of the domiphen is better.
Optionally, the concentration of the dihydrogen phosphate solution is 0.02 mol/L.
By adopting the technical scheme, the dihydrogen phosphate solution with proper concentration has proper buffer capacity, so that when the pH of the mobile phase is adjusted, the pH can be further finely adjusted within the range of 2-3.
In summary, the present application has at least one of the following advantages:
1. compared with the detection method of domiphen bromide in pharmacopoeia, the method adopts the C18 chromatographic column with low price and good universality, uses the mobile phase consisting of dihydrogen phosphate solution and acetonitrile, and ensures that the detection method of domiphen bromide has low cost, large detection linear range, small relative standard deviation and low detection limit by matching the chromatographic column and the mobile phase;
2. the method adopts ice bath ultrasound, and reduces the volatilization of the solvent by maintaining the low temperature during the ultrasound, thereby reducing the influence on the concentration of the domiphen bromide pretreatment solution and ensuring the accuracy and reliability of the detection result.
Drawings
FIG. 1 is a high performance liquid chromatogram with a domiphen bromide concentration of 0. mu.g/mL in detection limit;
FIG. 2 is a high performance liquid chromatogram with a domiphen bromide concentration of 100. mu.g/mL in detection limit;
FIG. 3 is a linear plot of domiphen bromide detection in the detection limit detection.
Detailed Description
The present application will be described in further detail with reference to examples and comparative examples.
The raw material sources are as follows: disinfecting gel, oral bacteriostatic spray, gynecological inflammation cleaning lotion, tinea pedis cleaning spray and baby skin-care gel, which are purchased from Hefei-pottery-one-class pharmaceutical biotechnology limited company; domiphen bromide standard, purchased from Shanghai Allantin Biotechnology, Inc.; monopotassium phosphate, acetonitrile, purchased from Shanghai Allantin Biotechnology Ltd; methanol and ethanol were purchased from Xian Hengtian chemical technology Co., Ltd.
Example 1
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
s1: pretreating a domiphen bromide disinfection product: placing 0.5g of domiphen bromide disinfection article in a 50mL volumetric flask, and dissolving with 20mL of methanol to obtain a domiphen bromide solution; filtering the domiphen bromide solution by using a filter membrane of 0.45 mu m to obtain a domiphen bromide sample solution;
s2: high performance liquid detection: taking 10 mu L of domiphen bromide sample solution, carrying out sample injection detection, adopting a C18 silane bonded silica gel column chromatographic column as the chromatographic column, adopting 0.02moL/L potassium dihydrogen phosphate solution-acetonitrile as a mobile phase, wherein the volume ratio of the potassium dihydrogen phosphate solution to the acetonitrile is 20: 85, the pH value of the mobile phase is 2.4, the detection wavelength is 269nm, and recording a chromatogram.
Example 2
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
the difference from example 1 is that, in the case of performing high performance liquid chromatography in S2, a C18 silane-bonded silica gel column was used as a column, and acetonitrile, which is a 0.02moL/L potassium dihydrogen phosphate solution, was used as a mobile phase, wherein 30mL of the potassium dihydrogen phosphate solution, 70mL of the acetonitrile (volume ratio: 30: 70), pH was 2.4, and the detection wavelength was 269 nm.
Example 3
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
the difference from example 1 is that, in the case of performing high performance liquid chromatography in S2, a C18 silane-bonded silica gel column was used as a column, and acetonitrile, which is a 0.02moL/L potassium dihydrogen phosphate solution, was used as a mobile phase, wherein the volume ratio of potassium dihydrogen phosphate solution was 24mL to acetonitrile 76mL (24: 76), the pH of the mobile phase was 2.4, and the detection wavelength was 269 nm.
Example 4
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
s1: a. pretreating a domiphen bromide disinfection product: placing 0.5g of domiphen bromide disinfection article in a 50mL volumetric flask, and dissolving with 20mL of methanol to obtain a domiphen bromide solution;
b. performing ultrasonic treatment on the domiphen bromide solution at room temperature for 20min to obtain a domiphen bromide pretreatment solution;
c. cooling the domiphen bromide pretreatment liquid to room temperature, and re-metering the volume to 20mL by using methanol to obtain a domiphen bromide standard liquid;
s2: high performance liquid detection: taking 10 mu L of domiphen bromide standard solution, carrying out sample injection detection, adopting a C18 silane bonded silica gel column chromatographic column as the chromatographic column, adopting 0.02moL/L potassium dihydrogen phosphate solution-acetonitrile as a mobile phase, wherein the volume ratio of the potassium dihydrogen phosphate solution to the acetonitrile is 30mL, the acetonitrile is 70mL (the volume ratio is 30: 70), the pH value is 2.4, the detection wavelength is 269nm, and recording a chromatogram.
Example 5
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
the difference from example 4 is that:
s1: and b, performing ice bath ultrasonic treatment on the domiphen bromide solution at the temperature of 0-10 ℃ for 20min to obtain a domiphen bromide pretreatment solution.
Example 6
The difference from embodiment 4 is that S1: and c, directly performing constant volume after the domiphen bromide pretreatment liquid in the step c is subjected to ultrasonic treatment, and cooling to room temperature is not needed.
The method comprises the following specific steps: c. and (4) re-metering the domiphen pre-treatment solution to 20mL by using methanol to obtain the domiphen standard solution.
Example 7
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
the difference from example 5 is that: the solvents are different;
the method comprises the following specific steps:
s1: a. pretreating a domiphen bromide disinfection product: placing 0.5g of domiphen bromide disinfection article in a 50mL volumetric flask, and dissolving with 20mL of ethanol to obtain a domiphen bromide solution;
c. and cooling the domiphen bromide pretreatment liquid to room temperature, and re-metering the volume to 20mL by using ethanol to obtain the domiphen bromide standard liquid.
Comparative example 1
The difference from example 5 is that: the pH of the mobile phase of step S2 was 8.
The method comprises the following specific steps: when high performance liquid detection is carried out in S2, 10 mu L of domiphen bromide sample solution is taken, sample injection detection is carried out, a C18 silane bonded silica gel column chromatographic column is adopted as the chromatographic column, 0.2moL/L potassium dihydrogen phosphate solution-acetonitrile is adopted as the mobile phase, wherein 24mL of potassium dihydrogen phosphate solution and 76mL of acetonitrile (volume ratio is 24: 76) are adopted as the mobile phase, the pH value of the mobile phase is 8, the detection wavelength is 269nm, and a chromatogram is recorded.
Comparative example 2
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
the difference from example 5 is that the column for efficient liquid phase detection in S2 adopts a C18 silane bonded silica gel column, and the mobile phase adopts 0.02moL/L potassium dihydrogen phosphate solution-acetonitrile, wherein the volume ratio of potassium dihydrogen phosphate solution is 10mL, acetonitrile is 90mL (10: 90), the pH of the mobile phase is 2.4, and the detection wavelength is 269 nm.
Comparative example 3
The method for measuring the domiphen bromide content is adopted under the item of Chinese pharmacopoeia domiphen dropping pill.
Comparative example 4
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
s1: taking about 5.0 g of sample, precisely weighing, placing in a conical flask with a plug, precisely sucking 50mL of mobile phase to dilute the sample, weighing, performing ultrasonic treatment for 15 min, weighing again, supplementing the mobile phase to reduce the mass loss, and filtering with a filter membrane to obtain a sample solution.
S2: high performance liquid detection: 10 mu L of sample solution is sampled, sample introduction detection is carried out, a C18 silane bonded silica gel column is adopted as a chromatographic column for high performance liquid detection, 0.012 mol/L sodium dodecyl sulfate-acetonitrile-methanol (volume ratio is 2: 6: 2) is adopted as a mobile phase, the detection wavelength is 275nm, and a chromatogram is recorded.
Comparative example 5
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
s1: taking the content of the product, precisely weighing a proper amount (about equivalent to 2.5 mg of domiphen bromide), placing the content in a 250mL volumetric flask, adding about 150mL of methanol, carrying out ultrasonic treatment for 15 min, cooling, adding methanol to dilute to a scale, shaking up, filtering, and taking a subsequent filtrate as a test solution.
S2: high performance liquid detection: taking 10 mu L of test solution, injecting sample for detection, carrying out high performance liquid detection on Agilent TC-C18 (4.6mm multiplied by 250mm, 5 mu m) as a chromatographic column, adjusting the pH value to 3.0 with 30% phosphoric acid solution (0.5% sodium dihydrogen phosphate) as a mobile phase and acetonitrile (the volume ratio is 25:75) as a mobile phase, and recording a chromatogram map when the detection wavelength is 269 nm.
Comparative example 6
The method for detecting the content of domiphen bromide in the disinfection product comprises the following detection steps:
the difference from example 5 is that: when high performance liquid detection is carried out in S2, 10 mu L of domiphen bromide sample solution is taken, sample injection detection is carried out, a C18 silane bonded silica gel column chromatographic column is adopted as the chromatographic column, 0.02moL/L potassium dihydrogen phosphate-methanol is adopted as the mobile phase, 25mL of potassium dihydrogen phosphate solution and 75mL of methanol (volume ratio is 25:75) are adopted as the mobile phase, the pH value of the mobile phase is 2.4, the detection wavelength is 275nm, and a chromatogram map is recorded.
Performance test
a. Detection limit detection
The detection steps are as follows:
s1: pretreating a domiphen bromide disinfection product: respectively placing the domiphen bromide standard samples with different weights into 50mL volumetric flasks, and dissolving the domiphen bromide standard samples with 20mL methanol to obtain domiphen bromide dissolving solutions with different concentrations; filtering the domiphen bromide solution by using a filter membrane of 0.45 mu m to obtain a domiphen bromide sample solution;
s2: high performance liquid detection: taking 10 mu L of domiphen bromide sample solution, carrying out sample injection detection, adopting a C18 silane bonded silica gel column as a chromatographic column, adopting 0.02moL/L potassium dihydrogen phosphate solution-acetonitrile as a mobile phase, wherein the volume ratio of the potassium dihydrogen phosphate solution to the acetonitrile is 20mL, the acetonitrile is 85mL (the volume ratio is 20: 85), the pH value of the mobile phase is 2.4, the detection wavelength is 269nm, and recording a chromatogram.
(domiphen bromide detection was performed with domiphen bromide solution of Table 1 and a linear relationship plot was plotted):
TABLE 1
| Concentration (μ g/mL) | 0 | 10 | 20 | 50 | 100 | 400 | 600 |
The method is adopted to detect the 50 mu g/mL domiphen bromide dissolving solution, instrument precision tests are carried out, and the test results are shown in Table 2:
TABLE 2
| Chromatographic peak area | Mean value of | RSD/% |
| 1.9125,1.8943,1.9051,1.8994,1.9213,1.8997,1.8969 | 1.9042 | 0.005059 |
Combining table 1 and table 2, it can be obtained that a standard working curve is drawn with the mass concentration (X) of domiphen bromide as abscissa and the corresponding chromatographic peak area (Y) as ordinate, wherein the chromatographic peak area (Y) is the average value of three detections, the linear equation is obtained as Y =0.1159X +3.1086, the limit range is 0-600 μ g/mL, R is2=0.999, the detection limit was calculated to be 0.0748 μ g/mL by the method of 3RSD/k (k is a low concentration slope).
The results of comparison of the detection limits of examples 3, 4, 5 and comparative examples 3, 4, 5, 6 of the present application are shown in table 3:
TABLE 3
| System of | Example 3 | Example 4 | Example 5 | Comparative example 3 | Comparative example 4 | Comparative example 5 | Comparative example 6 |
| Detection limit (μ g/mL) | 0.0748 | 0.0685 | 0.0579 | 0.7 | 0.13 | 2.03 | 1.5 |
Note: the detection method and calculation method of the detection limit in examples 4 and 5 and comparative examples 3, 4, 5 and 6 are the same as those of the detection limit in example 3.
As can be seen from table 3, in comparative examples 3, 4, 5 and 6, when domiphen bromide was detected without using a combination of a chromatographic column and a mobile phase, the detection limit was higher than that of the examples of the present application; example 4 differs from example 3 in that with the addition of an ultrasound operation, the detection limit of example 4 is lower than that of example 3; example 5 differs from example 4 in that the room-temperature ultrasonic operation was changed to the ice-bath ultrasonic operation, and the detection limit of example 5 was lower than that of example 4.
Analysis of actual samples
Different domiphen bromide sample solutions were prepared and tested according to the procedure of example 5, and the test results are shown in table 4:
TABLE 4
| Sample (I) | Domiphen bromide detection value | Quantity of indication |
| Disinfecting gel | 0.2043 | 0.15-0.25 |
| Oral cavity bacteriostatic spray liquid | 0.4122 | 0.3-0.5 |
| Fuyanjing lotion | 0.3694 | 0.3-0.5 |
| Tinea pedis and tinea pedis cleaning spray | 0.5825 | 0.3-0.7 |
| Skin-health gel for baby | 0.3412 | 0.2-0.4 |
Different actual samples are detected, the detection result is compared with a standard curve, and the obtained domiphen bromide detection values are all in the range of the sample marked amount, so that the standard curve is proved to be more accurate, and the obtained detection limit result is also more accurate.
Chromatogram analysis
The high performance liquid chromatography spectra obtained in examples 1 to 7 and comparative examples 1 to 6 were analyzed, and the retention time and tailing factor were counted. The statistical results are shown in table 5:
TABLE 5
| Detecting the index | Retention time | Tailing factor (r) |
| Example 1 | 0.51 | 1.11 |
| Example 2 | 0.46 | 1.12 |
| Example 3 | 0.44 | 1.08 |
| Example 4 | 0.43 | 1.04 |
| Example 5 | 0.43 | 1.01 |
| Example 6 | 0.46 | 1.10 |
| Example 7 | 0.66 | 1.56 |
| Comparative example 1 | 0.83 | 1.52 |
| Comparative example 2 | 1.5 | 1.42 |
| Comparative example 3 | 13.6 | 1.98 |
| Comparative example 4 | 6.8 | 1.56 |
| Comparative example 5 | 8.6 | 1.31 |
| Comparative example 6 | 10.5 | 2.3 |
By combining examples 1 and 2 and example 3, it can be seen that the matching of the mobile phase and the stationary phase in a certain volume ratio enables the detected peak speed of domiphen to be faster, the tailing factors are respectively 1.11, 1.12 and 1.08, and the peak shape is standard; when the volume ratio of the potassium dihydrogen phosphate solution to the acetonitrile is 24:75, the retention time is shortest and the tailing factor is smallest.
With reference to example 4 and example 3, since example 4 is different from example 3 in that ultrasonic operation is added to example 4, it can be seen that ultrasonic operation enables domiphen to have good dispersibility in methanol, and a tailing factor of a finally detected chromatographic peak is 1.04, which is closer to a peak shape of a standard domiphen peak than example 3, indicating that the ultrasonic operation effect is good.
By combining the example 5 and the example 4, it can be seen that the ice bath ultrasound is performed on the domiphen bromide detection sample in the example 5, so that the methanol solvent is difficult to volatilize during the ultrasound processing of the domiphen bromide sample, the domiphen bromide sample is dissolved in the methanol more thoroughly and uniformly, the tailing factor of the chromatographic peak obtained by final detection is 1.01, and is closest to the peak shape of the standard domiphen bromide peak, which indicates that the ice bath ultrasound effect is better.
By combining the embodiment 6 and the embodiment 5, it can be seen that, when the domiphen pretreatment solution is directly detected without cooling after ultrasonic treatment, the true domiphen standard solution concentration obtained by dissolving the domiphen in the solvent is different from the theoretical domiphen standard solution concentration due to more solvent volatilization, the standard property of the outgoing peak is greatly influenced, and the tailing factor is increased.
Combining example 7 and example 5, it can be seen that the sample solvent used in example 7 is ethanol, when ethanol is used as the sample solvent for sample detection, the chromatographic peak tailing factor of the domiphen sample is 1.14, and the peak-shaped tailing is more severe than that when the solvent is methanol, therefore, methanol is the best solvent for dissolving the domiphen sample.
Combining example 5 and comparative example 1, it can be seen that when the pH of the potassium dihydrogen phosphate solution becomes 8, there is a greater effect on the appearance of the domiphen bromide peak, the retention time is significantly prolonged, the tailing factor is greater than 1.5, and the tailing is severe.
Combining example 5 and comparative example 2, it can be seen that when the ratio of potassium dihydrogen phosphate solution to acetonitrile is out of the range of the ratio of the present application, the peak appearance of domiphen is greatly affected, the retention time is obviously prolonged, the tailing factor is 1.42, and the tailing is serious.
By combining example 5 with comparative examples 3, 4, 5, and 6, it can be seen that the retention times of the four detection methods are extended by about 15-25 times compared to the retention times of the present application, resulting in an extended time for detecting domiphen bromide and a greatly reduced detection efficiency; comparative example 3 is domiphen bromide detection performed according to pharmacopoeia, and compared with the method of the application, the tailing factor is large, and the tailing is serious; comparative examples 4, 5 and 6 were tested according to other methods of domiphen bromide detection in the industry, with other detection methods having severe tailing and nonstandard peak shape.
The present embodiment is only for explaining the present application, and it is not limited to the present application, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present application.
Claims (10)
1. The method for detecting the domiphen bromide content in the disinfection product is characterized by comprising the following steps:
s1: pretreating a domiphen bromide disinfection product: dissolving the domiphen bromide disinfectant with a solvent to obtain a domiphen bromide solution;
s2: high performance liquid detection: sampling 10 mu L, and carrying out sample injection detection, wherein the chromatographic column adopts a C18 silane bonded silica gel column, the mobile phase adopts dihydrogen phosphate solution-acetonitrile, and the volume ratio of the dihydrogen phosphate solution to the acetonitrile is (20-30): (70-85), the pH value of the mobile phase is 2-3, and the detection wavelength is 265-275 nm.
2. The method for detecting the domiphen bromide content in the disinfection article according to claim 1, wherein the volume ratio of the dihydrogen phosphate solution to the acetonitrile in the step S2 is (23-25): (75-77).
3. The method for detecting domiphen bromide content in a disinfection article of claim 1, wherein in S1, the solvent is methanol.
4. The method for detecting the domiphen bromide content in the disinfection article of claim 1, wherein the S1 further comprises a step of carrying out ultrasonic treatment on the domiphen bromide dissolving solution for 10-30min to obtain a domiphen bromide pretreatment solution.
5. The method of claim 4, wherein the step of S1 further comprises the steps of cooling the domiphen pre-treatment solution to room temperature, and re-diluting the volume with the solvent of S1 to the volume before sonication to obtain the domiphen standard solution.
6. The method for detecting the domiphen bromide content in the disinfection product as claimed in claim 4, wherein the ultrasonic treatment is ice bath ultrasonic, and the ultrasonic temperature is 0-10 ℃.
7. The method for detecting the domiphen bromide content in the disinfection article of any one of claims 1, 4, 5 or 6, wherein the S1 further comprises the step of filtering the domiphen bromide solution, the domiphen bromide pretreatment solution or the domiphen bromide standard solution by using a filter membrane smaller than or equal to 0.45 μm to obtain the domiphen bromide sample solution.
8. The method for detecting the domiphen bromide content in the disinfection article according to claim 1, wherein the pH of the mobile phase in step S2 is 2.3-2.5.
9. The method of claim 1, wherein the dihydrogen phosphate solution is one of sodium dihydrogen phosphate and potassium dihydrogen phosphate.
10. The method of claim 1 wherein the concentration of the dihydrogen phosphate solution is 0.02 mol/L.
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| JP2009507995A (en) * | 2005-07-28 | 2009-02-26 | インディアナ・ユニバーシティ・リサーチ・アンド・テクノロジー・コーポレーション | Niobium oxide compositions, nanostructures, bioactive forms and uses thereof |
| CN105954431A (en) * | 2016-07-11 | 2016-09-21 | 安徽联创生物医药股份有限公司 | Method for measuring substances relevant to ospemifene raw medicine through HPLC (high performance liquid chromatography) separation |
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