CN114720617A - Detection method for content of pyridine-3-sulfonyl chloride - Google Patents
Detection method for content of pyridine-3-sulfonyl chloride Download PDFInfo
- Publication number
- CN114720617A CN114720617A CN202210281107.2A CN202210281107A CN114720617A CN 114720617 A CN114720617 A CN 114720617A CN 202210281107 A CN202210281107 A CN 202210281107A CN 114720617 A CN114720617 A CN 114720617A
- Authority
- CN
- China
- Prior art keywords
- solution
- pyridine
- sulfonyl chloride
- acetonitrile
- mobile phase
- 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.)
- Pending
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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
-
- 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
- G01N30/88—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86
- G01N2030/8809—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample
- G01N2030/884—Integrated analysis systems specially adapted therefor, not covered by a single one of the groups G01N30/04 - G01N30/86 analysis specially adapted for the sample organic compounds
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)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
Abstract
The invention relates to a method for detecting the content of pyridine-3-sulfonyl chloride, which comprises the following steps: s1, derivatization: adding aniline and a pyridine-3-sulfonyl chloride sample to be tested into acetonitrile serving as a solvent, stirring and reacting when aniline is excessive, and diluting with an acetonitrile aqueous solution to obtain a test sample solution; s2, liquid chromatography detection: the chromatographic column uses octadecylsilane chemically bonded silica as a filler, an ultraviolet detector is adopted, 0.2 percent tetrabutylammonium hydroxide phosphate buffer solution is used as a mobile phase A, acetonitrile is used as a mobile phase B, the mobile phase A and the mobile phase B are mixed in proportion, then the sample solution is subjected to isocratic elution, the detection wavelength is 230nm, the flow rate is 0.5-1.5mL/min, the sample injection volume is 5-100 mu L, and the column temperature is 25-40 ℃. The method for detecting the content of the pyridine-3-sulfonyl chloride has the advantages of good accuracy and repeatability, strong specificity, high accuracy and simplicity in operation.
Description
Technical Field
The invention belongs to the field of organic matter analysis and detection, and particularly relates to a method for detecting the content of pyridine-3-sulfonyl chloride.
Background
Pyridine-3-sulfonyl chloride is a common medical intermediate, is colorless transparent liquid, is extremely unstable when meeting water, and is easy to hydrolyze to generate pyridine-3-sulfonic acid and hydrochloric acid, so that the pyridine-3-sulfonyl chloride loses activity. Can be used for synthesizing pyrimidine derivatives, and is an intermediate for synthesizing vonoprazan fumarate.
The current method for determining the content of pyridine-3-sulfonyl chloride is mainly titration (method for determining the content of pyridine-3-sulfonyl chloride patent application specification CN 201510220469.0). The method calculates the content of pyridine-3-sulfonyl chloride by titration of the total chlorine content and the amount of free acid in the pyridine-3-sulfonyl chloride. The titration method has the following disadvantages: 1) The specificity is poor, and when pyridine-3-sulfonyl chloride contains other impurities capable of dissociating chloride ions, the titration result is interfered. 2) In the titration process of the free acid, an ice-water mixture is required to be added to keep the solution of the test sample at 0 ℃, the process is easily influenced by the environmental temperature, and the water is added into the test sample, so that the test sample cannot be guaranteed not to generate hydrolysis reaction.
Disclosure of Invention
The invention aims to solve the technical problem of providing a method for detecting the content of pyridine-3-sulfonyl chloride, and aims to effectively detect the content of pyridine-3-sulfonyl chloride by liquid chromatography through a relatively thorough derivatization reaction, wherein the content of pyridine-3-sulfonyl chloride is stronger in specificity, higher in accuracy and relatively simple in operation.
The technical scheme for solving the technical problems is as follows: a method for detecting the content of pyridine-3-sulfonyl chloride comprises the following steps:
s1, derivatization: adding aniline and a pyridine-3-sulfonyl chloride sample to be detected into acetonitrile serving as a solvent, stirring and reacting when aniline is excessive, and diluting with an acetonitrile aqueous solution to obtain a sample solution; the unreacted pyridine-3-sulfonyl chloride reacts with water in the acetonitrile water solution added later to generate hydrochloric acid and pyridine-3-sulfonic acid;
s2, liquid chromatography detection: the chromatographic column uses octadecylsilane chemically bonded silica as a filler, an ultraviolet detector is adopted, 0.2 percent tetrabutylammonium hydroxide phosphate buffer solution is used as a mobile phase A, acetonitrile is used as a mobile phase B, the mobile phase A and the mobile phase B are mixed according to a ratio, and then a sample solution is subjected to isocratic elution, wherein the detection wavelength is 230nm, the flow rate is 0.5-1.5mL/min, the sample injection volume is 5-100 mu L, and the column temperature is 25-40 ℃.
On the basis of the technical scheme, the invention can be further improved as follows.
Specifically, the molar ratio of aniline to pyridine-3-sulfonyl chloride in S1 is 1.5-2.5: 1.
specifically, the volume fraction of acetonitrile in the acetonitrile aqueous solution in S1 is 50%, and the content of the pyridine-3-sulfonyl chloride sample to be detected in the test solution is 0.08-0.24 mg/mL.
Specifically, the specification of the chromatographic column in S2 is ACOSMOSIL C18-MS-II 5 μm 4.6X 250 mm.
Specifically, a 0.2% tetrabutylammonium hydroxide phosphate buffer solution in S2 was prepared from 20mL of 10% tetrabutylammonium hydroxide and 1.36g of potassium dihydrogen phosphate diluted with water to 1000mL and adjusted to pH 4.5 with phosphoric acid.
Specifically, in S2, the ratio of mobile phase a to mobile phase B is 62: 38 as a flow phase, the flow rate is 1mL/min, the sample injection volume is 10 muL, the running time is 10min, and the column temperature is 30 ℃.
Compared with the prior art, the invention has the beneficial effects that:
according to the method, the pyridine-3-sulfonyl chloride is subjected to derivatization by aniline, and then the derivatization product is subjected to liquid chromatography detection, so that the method is thorough in derivatization reaction, strong in specificity, high in accuracy and simple in operation, and the method for detecting the content of the pyridine-3-sulfonyl chloride has good accuracy and repeatability.
Drawings
FIG. 1 is a chromatogram (blank control) of a diluent detected by high performance liquid chromatography under set conditions according to the present invention;
FIG. 2 is a chromatogram obtained by detecting undivided sample diluent by high performance liquid chromatography under set conditions, and it can be seen that if pyridine-3-sulfonyl chloride is not completely derivatized, a peak of 3-pyridinesulfonic acid should be detected;
FIG. 3 is a chromatogram of the detection of pyridine-3-sulfonyl chloride after derivatization by HPLC detection under set conditions.
Detailed Description
The invention is described in further detail below with reference to the following figures and specific embodiments, which are given by way of illustration only and are not intended to limit the scope of the invention.
Setting the conditions of high performance liquid chromatography, wherein the used chromatographic column is ACOSMOSIL C18-MS-II 5 μm 4.6 × 250 mm; the mobile phase A is 0.2% tetrabutylammonium hydroxide phosphate buffer solution, 20mL of 10% tetrabutylammonium hydroxide and 1.36g of monopotassium phosphate are used for preparation, water is added for dilution to 1000mL, and the pH value is adjusted to 4.5 by phosphoric acid; the mobile phase B is acetonitrile, and the ratio of the mobile phases A and B in elution is preferably controlled to be 62: 38, the flow rate is preferably 1mL/min, the sample injection volume is 10 muL, the running time is 10min, the column temperature is 30 ℃, and the detection wavelength is 230 nm.
In the following examples, each solution used or tested accordingly was formulated as follows:
diluent agent: acetonitrile, 50% acetonitrile
1) Underivatized sample dilutions: weighing pyridine-3-sulfonyl chloride about 2mg, precisely weighing, placing in a 20mL measuring flask, adding the diluent to dilute to scale, and shaking up to obtain the final product.
2) Preparing a reference substance solution:
weighing about 20mg of 3-pyridine derivative reference substance, precisely weighing, placing into a 100mL measuring flask, adding 50% acetonitrile diluent for dissolving, diluting to scale, and shaking uniformly to obtain the final product (2 parts in parallel, namely reference substance solution 1 and reference substance solution 2 respectively).
3) Preparing a linear solution:
derivatizing agent (aniline acetonitrile solution): 20.0g of aniline was weighed and diluted to 500mL (40mg/mL) with acetonitrile,
linear stock solutions: weighing about 4.0g of sample, precisely weighing, diluting with acetonitrile in 100mL measuring flask to scale, shaking, and proportionally mixing (40mg/mL)
Linear solution 1: precisely measuring 2.5mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding aniline acetonitrile to dissolve the solution to ensure that the volume is 13mL, shaking the solution on a shaking instrument for 40min, adding 50% acetonitrile to dilute the solution to a scale, shaking the solution uniformly, measuring 1mL of the solution, placing the solution into a 50mL measuring flask, adding 50% acetonitrile to dilute the solution to a scale, and shaking the solution uniformly to obtain the aqueous solution (0.08 mg/mL).
Linear solution 2: precisely measuring 4mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding an aniline acetonitrile solution to ensure that the volume is 13mL, shaking the solution on a shaking instrument for 40min, adding 50% acetonitrile to dilute the solution to a scale, shaking the solution uniformly, measuring 2mL of the solution, placing the solution into a 100mL measuring flask, adding 50% acetonitrile to dilute the solution to a scale, and shaking the solution uniformly to obtain the compound (0.128 mg/mL).
Linear solution 3: precisely measuring 5mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding an aniline acetonitrile solution to ensure that the volume is 13mL, shaking the solution on a shaking instrument for 40min, adding 50% acetonitrile to dilute the solution to a scale, shaking the solution uniformly, measuring 2mL of the solution, placing the solution into a 100mL measuring flask, adding 50% acetonitrile to dilute the solution to a scale, and shaking the solution uniformly to obtain the compound (0.16 mg/mL).
Linear solution 4: precisely measuring 6mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding an aniline acetonitrile solution to ensure that the volume is 13mL, shaking the solution on a shaking instrument for 40min, adding 50% acetonitrile to dilute the solution to a scale, shaking the solution uniformly, measuring 2mL of the solution, placing the solution into a 100mL measuring flask, adding 50% acetonitrile to dilute the solution to a scale, and shaking the solution uniformly to obtain the compound (0.193 mg/mL).
Linear solution 5: precisely measuring 7.5mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding 13mL of aniline acetonitrile solution, shaking on a shaking instrument for 40min, adding 50% acetonitrile for dilution to scale, shaking up, measuring 2mL of the solution, placing the solution into a 100mL measuring flask, adding 50% acetonitrile for dilution to scale, and shaking up to obtain (0.24 mg/mL).
4) Preparing an accurate solution:
50% accuracy solution: precisely measuring 2.5mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding an aniline acetonitrile solution to ensure that the volume is 13mL, shaking for 40min on a shaking instrument, adding 50% acetonitrile for diluting to a scale, shaking uniformly, measuring 2mL of the solution, placing the solution into a 100mL measuring flask, adding 50% acetonitrile for diluting to a scale, and shaking uniformly to obtain the product.
(3 parts were prepared in parallel).
100% accuracy solution: weighing 5mL of linear stock solution densely, placing the linear stock solution in a 25mL measuring flask, adding an aniline acetonitrile solution to ensure that the volume is 13mL, shaking the solution on a shaking instrument for 40min, adding 50% acetonitrile to dilute the solution to a scale, shaking the solution evenly, weighing 2mL of the solution, placing the solution in a 100mL measuring flask, adding 50% acetonitrile to dilute the solution to a scale, and shaking the solution evenly to obtain the compound (3 parts in parallel).
150% accuracy solution: precisely measuring 7.5mL of linear stock solution, placing the linear stock solution into a 25mL measuring flask, adding an aniline acetonitrile solution to ensure that the volume is 13mL, shaking for 40min on a shaking instrument, adding 50% acetonitrile for diluting to a scale, shaking uniformly, measuring 2mL of the solution, placing the solution into a 100mL measuring flask, adding 50% acetonitrile for diluting to a scale, and shaking uniformly to obtain the compound (3 parts are prepared in parallel).
The following examples were performed using the conditions set forth above for high performance liquid chromatography to detect the diluent, the underivatized sample diluent, and the control solution 1, and the measured profiles are shown in fig. 1 to 3; then, carrying out system suitability verification, and carrying out detection by using a reference substance solution 1 and a reference substance solution 2, wherein the results are shown in table 1; finally, linearity and accuracy verification are performed, and the 50% linear solution, the 80% linear solution, the 100% linear solution, the 120% linear solution and the 150% linear solution are respectively detected, and the results are shown in the following tables 2 and 3.
TABLE 1 System suitability results
TABLE 2 Linear verification results
TABLE 3 accuracy verification results
As can be seen from the analysis of FIGS. 1 to 3 and tables 1 to 3, the method provided by the present invention for detecting the pyridine-3-sulfonyl chloride content has good accuracy, repeatability and system applicability.
The above description is only for the purpose of illustrating the preferred embodiments of the present invention and is not to be construed as limiting the invention, and any modifications, equivalents, improvements and the like that fall within the spirit and principle of the present invention are intended to be included therein.
Claims (6)
1. A method for detecting the content of pyridine-3-sulfonyl chloride is characterized by comprising the following steps:
s1, derivatization: adding aniline and a pyridine-3-sulfonyl chloride sample to be detected into acetonitrile serving as a solvent, stirring and reacting when aniline is excessive, and diluting with an acetonitrile aqueous solution to obtain a sample solution;
s2, liquid chromatography detection: the chromatographic column uses octadecylsilane chemically bonded silica as a filler, an ultraviolet detector is adopted, 0.2 percent tetrabutylammonium hydroxide phosphate buffer solution is used as a mobile phase A, acetonitrile is used as a mobile phase B, the mobile phase A and the mobile phase B are mixed in proportion, then the sample solution is subjected to isocratic elution, the detection wavelength is 230nm, the flow rate is 0.5-1.5mL/min, the sample injection volume is 5-100 mu L, and the column temperature is 25-40 ℃.
2. The method for detecting the content of pyridine-3-sulfonyl chloride according to claim 1, wherein the molar ratio of aniline to pyridine-3-sulfonyl chloride in S1 is 1.5-2.5: 1.
3. the method for detecting the content of pyridine-3-sulfonyl chloride according to claim 1, wherein the volume fraction of acetonitrile in the acetonitrile aqueous solution in S1 is 50%, and the content of a pyridine-3-sulfonyl chloride sample to be detected in the test solution is 0.08-0.24 mg/mL.
4. The method for detecting the content of pyridine-3-sulfonyl chloride as claimed in claim 1, wherein the specification of the chromatographic column in S2 is ACOSMOSIL C18-MS-II 5 μm 4.6X 250 mm.
5. The method of claim 1, wherein the 0.2% tetrabutylammonium hydroxide phosphate buffer solution in S2 is prepared by diluting 20mL of 10% tetrabutylammonium hydroxide and 1.36g potassium dihydrogen phosphate with water to 1000mL, and adjusting pH to 4.5 with phosphoric acid.
6. The method for detecting the content of pyridine-3-sulfonyl chloride as claimed in claim 1, wherein the ratio of mobile phase A to mobile phase B in S2 is 62: 38 as a flow phase, the flow rate is 1mL/min, the sample injection volume is 10 muL, the running time is 10min, and the column temperature is 30 ℃.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210281107.2A CN114720617A (en) | 2022-03-22 | 2022-03-22 | Detection method for content of pyridine-3-sulfonyl chloride |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210281107.2A CN114720617A (en) | 2022-03-22 | 2022-03-22 | Detection method for content of pyridine-3-sulfonyl chloride |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN114720617A true CN114720617A (en) | 2022-07-08 |
Family
ID=82239802
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN202210281107.2A Pending CN114720617A (en) | 2022-03-22 | 2022-03-22 | Detection method for content of pyridine-3-sulfonyl chloride |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN114720617A (en) |
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115219621A (en) * | 2022-07-14 | 2022-10-21 | 济南同路医药科技发展有限公司 | Method for quantitatively analyzing p-acetamido-benzenesulfonyl chloride based on derivatization method |
| CN116930370A (en) * | 2023-07-28 | 2023-10-24 | 辽源市百康药业有限责任公司 | Method for measuring parachloroaniline in paracetamol |
-
2022
- 2022-03-22 CN CN202210281107.2A patent/CN114720617A/en active Pending
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN115219621A (en) * | 2022-07-14 | 2022-10-21 | 济南同路医药科技发展有限公司 | Method for quantitatively analyzing p-acetamido-benzenesulfonyl chloride based on derivatization method |
| CN116930370A (en) * | 2023-07-28 | 2023-10-24 | 辽源市百康药业有限责任公司 | Method for measuring parachloroaniline in paracetamol |
| CN116930370B (en) * | 2023-07-28 | 2024-05-28 | 辽源市百康药业有限责任公司 | Method for measuring parachloroaniline in paracetamol |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN114720617A (en) | Detection method for content of pyridine-3-sulfonyl chloride | |
| Veazey et al. | Chemiluminescence high-performance liquid chromatographic detector applied to ascorbic acid determinations | |
| Bai et al. | Determination of lapatinib (GW572016) in human plasma by liquid chromatography electrospray tandem mass spectrometry (LC–ESI-MS/MS) | |
| CN106950306B (en) | Method for determining content of cysteine in compound amino acid injection | |
| CN107632076A (en) | The quick instrument analytical method of azanol residual quantity in a kind of reaction solution | |
| CN108872436B (en) | Method for analyzing content of D (-) p-hydroxyphenylglycine in D (-) p-hydroxyphenylglycine methyl ester | |
| CN109307716B (en) | Detection method of brexpiprazole related substance | |
| CN115656388B (en) | Method for detecting oseltamivir starting material and related substances thereof | |
| CN109142585B (en) | Method for detecting isomer of sodium pantothenate | |
| CN115266977B (en) | HPLC method for measuring DL-p-chlorostyrene ethyl ester content | |
| CN103175930B (en) | A kind of HPLC analytical method measuring sodium sulphite content | |
| CN112858524B (en) | Detection method and application of brexpiprazole related substance | |
| CN108872406B (en) | HPLC analysis detection method for related substances in aspartic acid bulk drug | |
| CN113607842A (en) | Method for identifying and measuring content of lactic acid in levofloxacin lactate | |
| CN110632197B (en) | Analysis and detection method for benzothiazole and derivatives thereof in dibenzothiazyl disulfide production process | |
| CN112129847A (en) | Method for detecting content of D-p-hydroxyphenylglycine methyl ester | |
| Peng et al. | A nitrogen-specific detector for high performance liquid chromatography | |
| CN113933424A (en) | Method for detecting impurities in apixaban starting material | |
| CN110988200A (en) | Analysis method of imidazole residue in recombinant human teriparatide for injection | |
| CN112305138B (en) | Method for simultaneously determining content of lysine and glycine | |
| CN112505194B (en) | Detection method of tebipenem pivoxil side chain and related substances thereof | |
| CN113030282B (en) | Method for analyzing and detecting substances related to phthalimide potassium salt | |
| CN113092622B (en) | Pretreatment method for detecting content of phenolic impurities in sample | |
| CN115267003B (en) | Method for detecting isomer content of S (-) -4-chloro-3-hydroxybutyric acid ethyl ester | |
| CN113884598A (en) | Method for determining trace glyoxylic acid in dichloroacetic acid by utilizing high performance liquid chromatography |
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 |