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CN-121978251-A - Detection method for determining impurity pyridine-3-sulfonic acid in voronoi fumarate tablet

CN121978251ACN 121978251 ACN121978251 ACN 121978251ACN-121978251-A

Abstract

The invention provides a detection method for determining impurity pyridine-3-sulfonic acid in a voronoi green sheet of fumaric acid, and relates to the technical field of medicine analysis and detection. The chromatographic condition is that the filler is octadecylsilane chemically bonded silica, the mobile phase A is ammonium acetate solution-sodium octanesulfonate-methanol, and the mobile phase B is methanol water solution, and the elution is carried out by adopting a gradient elution program. The detection method is stable and feasible, can effectively control the quality of the sample, and has reasonable design, strong operability, precision and reliability as shown by the research results of methodologies such as linear relation, precision, repeatability, recovery rate, durability and the like. The method has the characteristics of good specificity, high detection sensitivity, capability of realizing complete separation of impurity peaks and main peaks, capability of effectively eliminating matrix interference, realization of accurately quantifying target impurities, high sensitivity, good repeatability and simple operation, and greatly improves the quality control level of products.

Inventors

  • Li Yunqun
  • WEN ZHICONG
  • ZHUANG LIHONG
  • Cai Chunnuan

Assignees

  • 海南亚洲制药股份有限公司

Dates

Publication Date
20260505
Application Date
20260319

Claims (9)

  1. 1. A detection method for determining impurity pyridine-3-sulfonic acid in a voronoi green sheet of fumaric acid is characterized by adopting high performance liquid chromatography for determination, wherein the chromatographic condition is that a filler is octadecylsilane chemically bonded silica gel, a mobile phase A is ammonium acetate solution-sodium octanesulfonate-methanol, and a mobile phase B is methanol aqueous solution, and elution is carried out by adopting a gradient elution program.
  2. 2. The method for detecting pyridine-3-sulfonic acid impurity in voronoi green sheet as defined in claim 1, wherein the volume ratio of ammonium acetate solution-sodium octanesulfonate-methanol in mobile phase a is 92-94:1-3:5, and the volume concentration of aqueous methanol solution in mobile phase B is 50% -70%.
  3. 3. The method for detecting pyridine-3-sulfonic acid as defined in claim 2, wherein the volume ratio of ammonium acetate solution-sodium octanesulfonate-methanol in mobile phase A is 93:2:5, and the volume concentration of aqueous methanol solution in mobile phase B is 60%.
  4. 4. A method for determining the impurity pyridine-3-sulfonic acid in voronoi green sheet as defined in claim 3, wherein the concentration of the ammonium acetate solution is 25-30mmol/L.
  5. 5. A method for determining the impurity pyridine-3-sulfonic acid in voronoi diagram as set forth in claim 3, wherein the mobile phase a has a pH of 6.0 to 6.2.
  6. 6. The method for detecting pyridine-3-sulfonic acid impurity in voronoi green sheet as defined in claim 1, wherein the gradient elution procedure is as follows:
  7. 7. The method for detecting pyridine-3-sulfonic acid as defined in claim 1, wherein the chromatographic column is IncrtsilODS-3, the specification is 4.6mm×250mm,5 μm.
  8. 8. The method for detecting the impurity pyridine-3-sulfonic acid in the voronoi green sheet of fumaric acid according to claim 1, wherein the detection wavelength in the high performance liquid chromatography detection process is 260-265nm, the column temperature is 32-35 ℃ and the flow rate is 0.8-1.2mL/min.
  9. 9. The method for detecting pyridine-3-sulfonic acid as defined in claim 1, wherein the sample injection amount in the high performance liquid chromatography is 10 μl.

Description

Detection method for determining impurity pyridine-3-sulfonic acid in voronoi fumarate tablet Technical Field The invention relates to the technical field of medicine analysis and detection, in particular to a detection method for determining impurity pyridine-3-sulfonic acid in a voronoi cell. Background Fu Nuola (Vonoprazan Fumarate, TAK-438) fumaric acid is a novel oral potassium competitive acid blocker (P-CAB) with the chemical name 1- [5- (2-fluorophenyl) -1- (pyridine-3-sulfonyl) -1H-pyrrol-3-yl ] -N-methyl methylamine monofumarate, which can effectively inhibit the formation of mucosal lesions on the upper part of the gastrointestinal tract, and is used for treating reflux esophagitis and for eradicating helicobacter pylori in combination with appropriate antibiotics. The pyridine-3-sulfonyl chloride which is a key starting material for synthesizing the voronoi fumarate is a strong oxidant, has active chemical property and is easy to hydrolyze to generate pyridine-3-sulfonic acid, in addition, the voronoi fumarate can be degraded to obtain pyridine-3-sulfonic acid, and the impurity pyridine-3-sulfonic acid can be brought into a finished product to cause no therapeutic effect or influence the stability and the curative effect of a medicament, even has genetic toxicity, directly causes DNA damage and causes DNA mutation, thereby causing cancers and having potential safety hazards. Because the impurity pyridine-3-sulfonic acid has high polarity, and no ultraviolet characteristic absorption or weak absorption is generated in the weak alkaline drug matrix of the vonolamine fumarate, the conventional HPLC-UV method is difficult to directly perform effective separation and sensitive quantitative detection, and has poor repeatability. In addition, the prescription composition of the raw tablet of fumaric acid Fu Nuola is complex, and the auxiliary materials and the main components are easy to interfere the peak of pyridine-3-sulfonic acid, so that the quantification is inaccurate. Therefore, development of a detection method with high specificity, high sensitivity, poor anti-interference capability and simple operation is needed. Disclosure of Invention In view of the above, the invention provides a detection method for determining the impurity pyridine-3-sulfonic acid in a voronoi cell. The technical scheme of the invention is realized as follows: a detection method for determining impurity pyridine-3-sulfonic acid in a fumarated voronoi green sheet adopts high performance liquid chromatography to determine, wherein chromatographic conditions are that a filler is octadecylsilane chemically bonded silica, a mobile phase A is ammonium acetate solution-sodium octanesulfonate-methanol, and a mobile phase B is methanol aqueous solution, and elution is carried out by adopting a gradient elution program. Further, in the mobile phase A, the volume ratio of the ammonium acetate solution to the sodium octanesulfonate to the methanol is 92-94:1-3:5, and in the mobile phase B, the volume concentration of the methanol aqueous solution is 50-70%. Further, in the mobile phase A, the volume ratio of the ammonium acetate solution to the sodium octanesulfonate to the methanol is 93:2:5, and in the mobile phase B, the volume concentration of the aqueous methanol solution is 60%. Further, the concentration of the ammonium acetate solution is 25-30mmol/L. Further, the pH of the mobile phase A is 6.0-6.2. Further, the gradient elution procedure was: Further, the chromatographic column measured by the high performance liquid chromatography is IncrtsilODS-3, and the specification is 4.6mm multiplied by 250mm and 5 μm. Further, the detection wavelength in the high performance liquid chromatography measurement process is 260-265nm, the column temperature is 32-35 ℃ and the flow rate is 0.8-1.2mL/min. Further, the sample injection amount in the high performance liquid chromatography measurement process is 10 mu L. Compared with the prior art, the invention has the beneficial effects that: 1. The invention adopts a high performance liquid chromatograph (the mobile phase A is ammonium acetate solution-sodium octane sulfonate-methanol, the mobile phase B is methanol aqueous solution, and gradient elution is adopted) to establish a detection method of the impurity pyridine-3-sulfonic acid in the voronoi green sheet fumarate, the method is stable and feasible, the quality of the product can be effectively controlled, and the research results of methodologies such as alignment relation, precision, repeatability, recovery rate, durability and the like show that the method is reasonable in design, strong in operability, precise and reliable. 2. The method for detecting the impurity pyridine-3-sulfonic acid in the voronoi green sheet of fumaric acid has the characteristics of good specificity, high detection sensitivity, capability of realizing complete separation of an impurity peak and a main peak, capability of effectively eliminating mat