CN114216985A - Method for testing diisopropyl sulfate in isosorbide - Google Patents
Method for testing diisopropyl sulfate in isosorbide Download PDFInfo
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- CN114216985A CN114216985A CN202111568989.2A CN202111568989A CN114216985A CN 114216985 A CN114216985 A CN 114216985A CN 202111568989 A CN202111568989 A CN 202111568989A CN 114216985 A CN114216985 A CN 114216985A
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- HWBLTYHIEYOAOL-UHFFFAOYSA-N Diisopropyl sulfate Chemical compound CC(C)OS(=O)(=O)OC(C)C HWBLTYHIEYOAOL-UHFFFAOYSA-N 0.000 title claims abstract description 74
- KLDXJTOLSGUMSJ-JGWLITMVSA-N Isosorbide Chemical compound O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 KLDXJTOLSGUMSJ-JGWLITMVSA-N 0.000 title claims abstract description 41
- 229960002479 isosorbide Drugs 0.000 title claims abstract description 41
- 238000000034 method Methods 0.000 title claims abstract description 26
- 238000012360 testing method Methods 0.000 title description 4
- 238000001514 detection method Methods 0.000 claims abstract description 16
- 239000000243 solution Substances 0.000 claims description 100
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 claims description 18
- 239000012085 test solution Substances 0.000 claims description 13
- 239000012088 reference solution Substances 0.000 claims description 12
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 10
- 239000012490 blank solution Substances 0.000 claims description 10
- 230000035945 sensitivity Effects 0.000 claims description 9
- 238000010438 heat treatment Methods 0.000 claims description 7
- 238000001212 derivatisation Methods 0.000 claims description 6
- 239000012483 derivatization solution Substances 0.000 claims description 6
- 238000004817 gas chromatography Methods 0.000 claims description 6
- 235000009518 sodium iodide Nutrition 0.000 claims description 6
- 229960005070 ascorbic acid Drugs 0.000 claims description 5
- 235000010323 ascorbic acid Nutrition 0.000 claims description 5
- 239000011668 ascorbic acid Substances 0.000 claims description 5
- 239000007788 liquid Substances 0.000 claims description 5
- 239000012159 carrier gas Substances 0.000 claims description 3
- -1 dimethylsiloxane Chemical class 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 238000011067 equilibration Methods 0.000 claims description 2
- 238000002347 injection Methods 0.000 claims description 2
- 239000007924 injection Substances 0.000 claims description 2
- 239000007864 aqueous solution Substances 0.000 claims 1
- 238000005220 pharmaceutical analysis Methods 0.000 abstract description 2
- 239000003085 diluting agent Substances 0.000 description 46
- 239000000203 mixture Substances 0.000 description 23
- 238000007789 sealing Methods 0.000 description 19
- 239000011550 stock solution Substances 0.000 description 18
- 238000007664 blowing Methods 0.000 description 11
- 238000003260 vortexing Methods 0.000 description 11
- 238000005303 weighing Methods 0.000 description 8
- 238000001035 drying Methods 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- 238000007865 diluting Methods 0.000 description 6
- 238000000926 separation method Methods 0.000 description 6
- 238000010790 dilution Methods 0.000 description 5
- 239000012895 dilution Substances 0.000 description 5
- 238000011084 recovery Methods 0.000 description 5
- 238000001816 cooling Methods 0.000 description 4
- 230000004044 response Effects 0.000 description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 3
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- 238000007605 air drying Methods 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 210000001175 cerebrospinal fluid Anatomy 0.000 description 2
- 230000018044 dehydration Effects 0.000 description 2
- 238000006297 dehydration reaction Methods 0.000 description 2
- 238000004090 dissolution Methods 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 238000002290 gas chromatography-mass spectrometry Methods 0.000 description 2
- 231100000025 genetic toxicology Toxicity 0.000 description 2
- 230000001738 genotoxic effect Effects 0.000 description 2
- 239000012535 impurity Substances 0.000 description 2
- 229960003827 isosorbide mononitrate Drugs 0.000 description 2
- YWXYYJSYQOXTPL-SLPGGIOYSA-N isosorbide mononitrate Chemical compound [O-][N+](=O)O[C@@H]1CO[C@@H]2[C@@H](O)CO[C@@H]21 YWXYYJSYQOXTPL-SLPGGIOYSA-N 0.000 description 2
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 2
- 230000003204 osmotic effect Effects 0.000 description 2
- 238000011002 quantification Methods 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 206010048962 Brain oedema Diseases 0.000 description 1
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 description 1
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 1
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 description 1
- 208000010412 Glaucoma Diseases 0.000 description 1
- 229930195725 Mannitol Natural products 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 230000009471 action Effects 0.000 description 1
- 229940047033 ascorbic acid 10 mg Drugs 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
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- 210000004556 brain Anatomy 0.000 description 1
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- 230000008859 change Effects 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 239000002537 cosmetic Substances 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 239000002934 diuretic Substances 0.000 description 1
- 230000001882 diuretic effect Effects 0.000 description 1
- 210000001508 eye Anatomy 0.000 description 1
- 235000013305 food Nutrition 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 238000007917 intracranial administration Methods 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 239000000594 mannitol Substances 0.000 description 1
- 235000010355 mannitol Nutrition 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
- G01N30/62—Detectors specially adapted therefor
- G01N30/64—Electrical detectors
- G01N30/70—Electron capture 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
- G01N2030/022—Column chromatography characterised by the kind of separation mechanism
- G01N2030/025—Gas 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
- G01N2030/067—Preparation by reaction, e.g. derivatising the sample
Abstract
The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for detecting diisopropyl sulfate in isosorbide, which is a convenient, efficient and accurate detection method for solving the problem of detection of diisopropyl sulfate in isosorbide.
Description
Technical Field
The invention belongs to the technical field of pharmaceutical analysis, and particularly relates to a method for testing diisopropyl sulfate in isosorbide.
Background
Isosorbide is a bio-based functional diol, is an important bio-based platform molecule, can be applied to the fields of medicines, foods, cosmetics and the like, is taken as a dehydration derivative of sorbitol, is an oral osmotic dehydration diuretic, has an action mechanism similar to intravenous injection of mannitol and sorbitol, and can be used for treating cerebral edema and glaucoma by increasing the osmotic pressure of blood plasma and leading water in tissues (including eyes, brain, cerebrospinal fluid and the like) to enter blood vessels so as to relieve edema, reduce the intraocular pressure, the intracranial pressure, the cerebrospinal fluid volume and the pressure thereof.
Sulfuric acid and isopropanol are used in the synthesis process of the isosorbide, diisopropyl sulfate can be generated and can remain in the isosorbide, and the structural formula of the diisopropyl sulfate is as follows:
the diisopropyl sulfate comprises a genotoxicity warning structure, the maximum daily dose of isosorbide mononitrate is 120mg according to the limit TTC of the genetic impurity in ICH M7 calculated according to 1.5 ug/day, the limit of the diisopropyl sulfate in the finished product isosorbide mononitrate is calculated according to the formula limit = TTC/maximum daily dose, and the control on the genotoxicity impurity diisopropyl sulfate in isosorbide is required to ensure the medication safety.
Diisopropyl sulfate has no ultraviolet absorption, the limit is extremely low, the determination is difficult, the document reports that the diisopropyl sulfate residue in a sample is determined by a liquid chromatography-mass spectrometry method or the diisopropyl sulfate residue in the sample is determined by a GC-MS method, and the LC-MS and GC-MS have high sensitivity and high price.
The invention uses gas chromatography to determine diisopropyl sulfate in isosorbide, uses derivatization solution to perform pre-column derivatization, uses an ECD detector to perform separation determination of diisopropyl sulfate in isosorbide, has better sensitivity on the ECD detector, and has lower detection limit compared with a method without pre-column derivatization.
Disclosure of Invention
The invention provides a method for detecting diisopropyl sulfate in isosorbide, which can be used for solving the problem of detecting diisopropyl sulfate in isosorbide and providing a convenient, efficient and accurate detection method.
In order to achieve the purpose, the invention provides the following technical scheme:
a method for detecting diisopropyl sulfate in isosorbide comprises the steps of measuring diisopropyl sulfate in isosorbide by using a gas chromatography, carrying out pre-column derivatization by using a derivatization solution, and carrying out separation and measurement on diisopropyl sulfate in isosorbide by using an ECD detector, wherein the detection method comprises the following steps:
(1) preparing a solution, and respectively preparing a blank solution, a system applicability solution, a derivative solution and a test solution.
(2) The determination method comprises the following steps: measuring diisopropyl sulfate in isosorbide by adopting a gas chromatography, respectively feeding a blank solution, a sensitivity solution, a reference solution and a test solution after a system is stabilized, and recording a chromatogram;
the chromatographic conditions are as follows, the gas chromatograph is provided with an ECD detector and a chromatographic column: capillary column with 6% cyanopropylphenyl-94% dimethylsiloxane as stationary liquid, column temperature: keeping the temperature at 70 ℃ for 0min, heating to 150 ℃ at 5 ℃/min, keeping the temperature for 0min, and adding a sample inlet: 220 ℃, detector temperature: at 250 ℃, the split ratio: 10: 1, carrier gas: n2, flow rate: 1.5ml/min, injection volume: 1ml, headspace equilibrium temperature: 80 ℃, equilibration time: and (4) 40 min.
Further, the column was DB-62430 m × 0.53mm, 3.0 μm, derivatization solution: taking a proper amount of sodium iodide and ascorbic acid, placing the sodium iodide and the ascorbic acid into a measuring flask, adding a proper amount of water for dissolving, diluting to a scale, and shaking up; blank solution: taking a proper amount of diluent and derivative solution, placing in a headspace bottle, covering and sealing, after vortex, placing in an air-blast drying oven, heating at 80 ℃ for 1 hour, and cooling to room temperature; diluting liquid: acetonitrile; reference solution: taking a proper amount of diluent and diisopropyl sulfate stock solution, placing the diluent and the diisopropyl sulfate stock solution into a measuring flask, adding the diluent to dilute the solution to a scale, and shaking up the solution; transferring appropriate amount of the above solution and derivative solution, placing in a headspace bottle, sealing with a cover, vortex, heating in a forced air drying oven at 80 deg.C for 1 hr, cooling, and standing at room temperature; diisopropyl sulfate stock solution: placing a proper amount of diluent in a measuring flask, taking a proper amount of diisopropyl sulfate, adding the diluent to dilute to a scale, and shaking up; sensitivity solution: placing an appropriate amount of diluent in a measuring flask, placing an appropriate amount of diisopropyl sulfate stock solution in the measuring flask, adding the diluent to dilute to a scale, and shaking up; transferring appropriate amount of the above solution and derivative solution, placing in a headspace bottle, sealing with a cover, vortex, heating in a forced air drying oven at 80 deg.C for 1 hr, cooling, and standing at room temperature; test solutions: taking a proper amount of isosorbide sample, placing the isosorbide sample in a measuring flask, adding a proper amount of diluent to dissolve and dilute the isosorbide sample to a scale, and shaking up the isosorbide sample; transferring appropriate amount of the above solution and derivative solution, placing in a headspace bottle, sealing with a cover, vortex, heating in an air-blast drying oven at 80 deg.C for 1 hr, cooling, and standing at room temperature.
To ensure the accuracy of this method, the methodology was validated: the system applicability, specificity (separation degree and sample adding recovery), detection limit and quantification limit, linearity and range, precision and solution stability are as follows:
the invention uses gas chromatography to determine diisopropyl sulfate in isosorbide, uses derivatization solution to perform pre-column derivatization, uses an ECD detector to perform separation determination of diisopropyl sulfate in isosorbide, has better sensitivity on the ECD detector, and has lower detection limit compared with a method without pre-column derivatization.
Drawings
FIG. 1 is a blank solution profile of the present invention
FIG. 2 is a reference solution spectrum of the present invention
FIG. 3 is a test solution profile of the present invention
FIG. 4 is a map of the applicability of the system of the present invention
Detailed Description
The invention is further illustrated by the following examples, which are not to be construed as limiting the invention thereto.
Example 1:
(1) preparing a solution:
diluting liquid: acetonitrile;
derivatization solution: taking 60g of sodium iodide and 1g of ascorbic acid, precisely weighing, placing in a 100ml measuring flask, adding a proper amount of water for dissolving, diluting to a scale, and shaking uniformly. (concentration: sodium iodide 600mg/ml, ascorbic acid 10 mg/ml)
Blank solution: precisely measuring 4.0ml of the diluent and 1.0ml of the derivative solution, placing in a 20ml headspace bottle, and capping and sealing; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: sodium iodide 120mg/ml, ascorbic acid 2 mg/ml)
Diisopropyl sulfate stock solution: taking a 20ml measuring flask, adding an appropriate amount of diluent, taking about 25mg of diisopropyl sulfate, precisely weighing, adding the diluent to dilute to a scale, and shaking up; taking a 200ml measuring flask, adding an appropriate amount of diluent, precisely transferring 5.0ml of the solution into the flask, adding the diluent to dilute to a scale, and shaking up; taking a 200ml measuring flask, adding an appropriate amount of diluent, precisely transferring 5.0ml of the solution into the flask, adding the diluent to dilute to a scale, and shaking up. (concentration: 0.7812. mu.g/ml)
Reference solution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 10.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0625. mu.g/ml)
Sensitivity solution: taking a 50ml measuring flask, adding an appropriate amount of diluent, precisely transferring 5.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; taking a 20ml measuring flask, adding an appropriate amount of diluent, precisely transferring 5.0ml of the solution, placing the solution in the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0156. mu.g/ml)
Test solutions: taking an isosorbide sample of about 125mg, precisely weighing, placing in a 20ml measuring flask, adding a proper amount of diluent for dissolving and diluting to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: isosorbide 5.0 mg/ml)
Selective solution: taking an isosorbide sample of about 125mg, precisely weighing, placing in a 20ml measuring flask, adding a proper amount of diluent for dissolution, precisely transferring 2.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent for dilution to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0625. mu.g/ml, isosorbide 5.0 mg/ml)
Test solutions (spiked): taking an isosorbide sample of about 125mg, precisely weighing, placing in a 20ml measuring flask, adding a proper amount of diluent for dissolution, precisely transferring 2.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent for dilution to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after being swirled for 1 minute, the mixture is placed in a blast drying oven to be heated for 1 hour at the temperature of 80 ℃, and then is cooled and placed at the room temperature; 6 portions of the mixture are prepared by the same method. (concentration: diisopropyl sulfate 0.0625. mu.g/ml, isosorbide 5.0 mg/ml)
LOQ solution: adjusting the dilution ratio according to the S/N value of diisopropyl sulfate obtained by the sensitivity solution until the S/N value of diisopropyl sulfate is more than or equal to 10; after the solution is swirled for 1 minute, the solution is placed in a blast drying oven to be heated for 1 hour at the temperature of 80 ℃, and then the solution is cooled and placed at the room temperature; 6 portions of the mixture are prepared by the same method.
LOD solution: precisely transferring 6.0ml of LOQ solution, placing the LOQ solution in a 20ml volumetric flask, adding diluent to dilute the LOQ solution to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature.
linear-LOQ solution: see LOQ solution preparation under the quantitative limit and detection limit terms.
Linear 50% solution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 5.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0312. mu.g/ml)
Linear 80% solution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 8.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0500. mu.g/ml)
Linear 100% solution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 10.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0625. mu.g/ml)
Linear 120% solution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 12.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0750. mu.g/ml)
Linear 150% solution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 15.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after vortexing for 1 minute, the mixture was heated in an air-blowing dry oven at 80 ℃ for 1 hour, and then cooled to room temperature. (concentration: diisopropyl sulfate 0.0937. mu.g/ml)
Accuracy LOQ stock: preparing an LOQ solution according to the quantitative limit and the detection limit; 3 portions of the mixture are prepared by the same method.
Accuracy 150% dilution: taking a 100ml measuring flask, adding an appropriate amount of diluent, precisely transferring 15.0ml of the diisopropyl sulfate stock solution into the flask, adding the diluent to dilute to a scale, and shaking up; 3 portions of the mixture are prepared by the same method. (concentration: 0.0937. mu.g/ml)
Accuracy LOQ solutions: precisely weighing an appropriate amount of isosorbide sample, placing the isosorbide sample in a measuring flask, adding an appropriate amount of diluent to dissolve the isosorbide sample, precisely transferring an appropriate amount of the accurate LOQ stock solution to the flask, adding the diluent to dilute the stock solution to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing in a 20ml headspace bottle, covering and sealing, and shaking up; preparing a solution with 5mg/ml of isosorbide and LOQ concentration of diisopropyl sulfate; after being swirled for 1 minute, the mixture is placed in a blast drying oven to be heated for 1 hour at the temperature of 80 ℃, and then is cooled and placed at the room temperature; 3 portions of the mixture are prepared by the same method.
Accuracy 150% solution: taking an isosorbide sample of about 125mg, precisely weighing, placing in a 20ml measuring flask, adding a proper amount of diluent with accuracy of 150%, dissolving and diluting to a scale, and shaking up; precisely transferring 4.0ml of the solution and 1.0ml of the derivative solution, placing the solution in a 20ml headspace bottle, and covering and sealing the bottle; after being swirled for 1 minute, the mixture is placed in a blast drying oven to be heated for 1 hour at the temperature of 80 ℃, and then is cooled and placed at the room temperature; 3 portions of the mixture are prepared by the same method. (concentration: diisopropyl sulfate 0.0937. mu.g/ml, isosorbide 5.0 mg/ml)
(2) Chromatographic conditions are as follows:
the instrument comprises the following steps: the gas chromatograph is provided with an ECD detector, a headspace automatic sample injector and an electronic analytical balance.
A chromatographic column: capillary column using 6% cyanopropylphenyl-94% dimethyl siloxane as stationary liquid (such as DB-62430 m × 0.53mm, 3.0 μm or equivalent polarity chromatography column)
Column temperature: keeping at 70 deg.C for 0min, heating to 150 deg.C at 5 deg.C/min, and keeping for 0 min;
sample inlet temperature: 220 ℃; detector temperature: 250 ℃;
the split ratio is as follows: 10: 1; carrier gas: n2;
flow rate: 1.5 ml/min; sample introduction volume: 1 ml;
headspace equilibrium temperature: 80 ℃; the balance time is as follows: 40 min;
remarking: then the operation is carried out at 240 ℃ for 5min, and the flow is 3 ml/min;
(3) the determination method comprises the following steps:
and after the system is stable, feeding a blank solution 1 needle, a sensitivity solution 1 needle, a reference solution 6 needle and a test solution 1 needle, and recording a chromatogram.
And (3) calculating:
diisopropyl sulfate (ppm) = (RU/Rs) × (Cs/CU)
Wherein: RU: testing the peak area of diisopropyl sulfate in a solution map;
rs: the average peak area of diisopropyl sulfate in 6-pin reference solution spectra;
cs: the concentration of diisopropyl sulfate in the reference solution (. mu.g/ml);
CU: the concentration of the solution (g/ml) was tested.
Example 2: system applicability
The system applicability is realized by measuring the S/N value of diisopropyl sulfate in a sensitive solution and the RSD of the diisopropyl sulfate peak area in 6-pin reference solution; the S/N value of diisopropyl sulfate in the sensitive solution and the RSD of the diisopropyl sulfate peak area in 6-pin reference solution were required to meet the acceptance criteria.
Example 3: specificity
The specificity is that the blank solution is determined to have no interference to the detection of the diisopropyl sulfate; the separation degree between diisopropyl sulfate and adjacent chromatographic peaks in the selective solution; the blank solution should not interfere with the detection of diisopropyl sulfate, and the separation degree between diisopropyl sulfate and adjacent chromatographic peaks in the selective solution should meet the acceptable standard.
Example 4: precision degree
Repeatability: reproducibility was achieved by measuring the RSD of the diisopropyl sulfate assay in 6 test solutions (spiked) requiring that the RSD of the diisopropyl sulfate assay in 6 test solutions (spiked) should meet acceptable standards.
Example 5: detection limit and quantification limit
The detection limit is obtained by detecting the ratio (S/N) ≧ 3 of the response signal to the noise, and the quantitative limit is obtained by detecting the ratio (S/N) ≧ 10 of the response signal to the noise. At the concentration level, 6 parts of LOQ solution are repeatedly examined, and the RSD of the unit concentration peak area of diisopropyl sulfate in the 6 parts of LOQ solution is required to meet the acceptable standard to confirm that the determination result of the limit of quantitation has certain precision.
Example 6: linearity and range
Selecting 6 concentration points within the range of LOQ-150% limit concentration, drawing a curve by taking the concentration as an abscissa and taking a peak area as an ordinate, and requiring that the ratio of the square of a linear correlation coefficient (R2) of the curve and the absolute value of a y-axis intercept to a response value of 100% concentration meets an acceptable standard.
Example 7: accuracy of
Accuracy is achieved by determining the recovery and total RSD of recovery (n = 9) between the measured concentration and the theoretical concentration of the measured component, requiring that the recovery and total RSD of recovery (n = 9) of the measured component over each concentration range should meet acceptable standards.
Example 8: durability
The reference solution, the test solution and the selective solution are inspected to be injected when being placed at room temperature for a period of time, the change rule of the detection result along with time is inspected, and a basis is provided for the placing time of the reference solution and the test solution during detection
Claims (2)
1. A method for detecting diisopropyl sulfate in isosorbide is characterized in that gas chromatography is used for detecting diisopropyl sulfate in isosorbide, derivatization solution is used for pre-column derivatization, an ECD detector is used for separating and detecting the diisopropyl sulfate in isosorbide, and the detection method comprises the following steps:
(1) preparing solutions, namely respectively preparing a blank solution, a system applicability solution, a derivative solution and a test solution;
(2) the determination method comprises the following steps: measuring diisopropyl sulfate in isosorbide by adopting a gas chromatography, respectively feeding a blank solution, a sensitivity solution, a reference solution and a test solution after a system is stabilized, and recording a chromatogram;
the chromatographic conditions are as follows, the gas chromatograph is provided with an ECD detector and a chromatographic column: capillary column with 6% cyanopropylphenyl-94% dimethylsiloxane as stationary liquid, column temperature: keeping the temperature at 70 ℃ for 0min, heating to 150 ℃ at 5 ℃/min, keeping the temperature for 0min, and adding a sample inlet: 220 ℃, detector temperature: at 250 ℃, the split ratio: 10: 1, carrier gas: n2, flow rate: 1.5ml/min, injection volume: 1ml, headspace equilibrium temperature: 80 ℃, equilibration time: and (4) 40 min.
2. The method of claim 1, wherein:
the chromatographic column is DB-62430 m × 0.53mm, 3.0 μm, and the derivative solution is aqueous solution of sodium iodide and ascorbic acid.
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