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CN-122017098-A - Method for detecting paracetamol in compound paracetamol and chlorphenamine maleate granules and application thereof

CN122017098ACN 122017098 ACN122017098 ACN 122017098ACN-122017098-A

Abstract

The invention provides a detection method and application of paracetamol in compound paracetamol and chlorphenamine maleate granules, and belongs to the technical field of chemical drug analysis methods. The invention discloses a method for detecting paracetamol in compound paracetamol and chlorphenamine maleate granules, which is a high performance liquid chromatography, wherein the high performance liquid chromatography comprises a chromatographic column which is octadecylsilane chemically bonded silica gel, detection wavelength of 255-259nm, flow rate of 0.9-1.1ml/min, column temperature of 28-32 ℃, a mobile phase A which is 0.025mol/L disodium hydrogen phosphate solution (pH is regulated to 6.6 by phosphoric acid), a mobile phase B which is methanol, and a gradient elution separation process, wherein a solvent is 15% methanol water (containing 0.1mg/ml ascorbic acid) solution. The analytical method can accurately and quantitatively detect the paracetamol in the compound paracetamol and chlorphenamine maleate granules, and the separation degree of the paracetamol peak and the adjacent impurity peak meets the requirements.

Inventors

  • JIA XIAORUI
  • YAN YUNFEI
  • DAI QIAN
  • Feng Xiaodai
  • YANG LIN
  • WU MENG
  • Wang Dansai

Assignees

  • 河北长天药业有限公司

Dates

Publication Date
20260512
Application Date
20260204

Claims (8)

  1. 1. A method for detecting paracetamol in compound paracetamol granules is characterized by adopting a high performance liquid chromatography, wherein the chromatographic conditions are as follows: Preferably, the chromatographic column is Welch Xtimate ® C18.6X105 mm,5 μm or Thermo Acclaim TM C18.6X105 mm,5 μm; The flow rate is 0.9-1.1mL/min, preferably 1.0mL/min; The column temperature is 28-32 ℃, preferably 30 ℃; The detection wavelength is 255-259nm; Mobile phase: Mobile phase A is disodium hydrogen phosphate solution; Mobile phase B, methanol; solvent 15% methanol water solution; the elution mode is gradient elution, and the gradient elution is as follows: 0-15min, 92% -88% of mobile phase A is changed to 75%, 8% -12% of mobile phase B is changed to 25%; 15-30min, 75% of mobile phase A is changed to 45%, and 25% of mobile phase B is changed to 55%; 30-44min, 45% of mobile phase A and 55% of mobile phase B; 44.1-55min, 92-88% of mobile phase A and 8-12% of mobile phase B.
  2. 2. The method according to claim 1, wherein the mobile phase A is disodium hydrogen phosphate solution with pH of 6.6.
  3. 3. The method according to claim 2, wherein the disodium hydrogen phosphate solution has a concentration of 0.025mol/L.
  4. 4. The method according to claim 1, wherein the volume fraction of methanol and water in the solvent is 15% -85%.
  5. 5. The method according to claim 1, wherein ascorbic acid is added as a stabilizer to the solvent at a concentration of 0.1mg/ml.
  6. 6. The method of claim 1, wherein the gradient elution is:
  7. 7. The method according to any one of claims 1 to 8, comprising the steps of: (1) And (3) accurately weighing a proper amount of the para-aminophenol reference substance, and adding a solvent to quantitatively dilute the para-aminophenol reference substance into a solution with the concentration of 0.5 mg/ml. (2) The reference substance solution is prepared by taking the para-aminophenol reference substance, adding a solvent and quantitatively diluting to 5 mug/ml. (3) Grinding compound paracetamol and chlorphenamine maleate granules, adding a solvent, quantitatively diluting to obtain a solution with paracetamol concentration of 5mg/ml, and taking a subsequent filtrate. (4) Grinding compound paracetamol particles, precisely measuring a proper amount of a storage solution of a paracetamol reference substance, adding a solvent, quantitatively diluting into a solution containing 5mg/ml of paracetamol and 50 mug/ml of paracetamol, and taking a subsequent filtrate. (5) Respectively measuring 20 μl of reference solution, sample solution, and sample+impurity solution, and injecting into liquid chromatograph for detection.
  8. 8. Use of the detection method according to any one of claims 1-7 in quality control of a compound paracetamol granule.

Description

Method for detecting paracetamol in compound paracetamol and chlorphenamine maleate granules and application thereof Technical Field The invention relates to a method for detecting paracetamol in compound paracetamol and chlorphenamine maleate granules, and relates to the technical field of chemical drug analysis methods. Background The purity of the medicine can reflect the quality of the medicine, and related substances are main factors influencing the purity of the medicine, and are mainly substances such as starting materials, reagents, intermediates, byproducts and the like brought in the production process of the medicine, and special impurities such as degradation products, polymers or crystal form transformation and the like generated in the production, transportation and storage processes. Different synthesis routes and different production processes of the medicine can produce different related substances, so that a scientific and perfect detection method needs to be established, and the aim of accurately detecting and monitoring all related substances of the medicine is fulfilled. The compound paracetamol and chlorphenamine maleate granules are an anti-cold medicine, are compound preparations, and can effectively relieve various symptoms caused by cold, such as fever, headache, sore throat, nasal obstruction, runny nose, sneeze and the like. Wherein the main components are acetaminophen, chlorpheniramine maleate, artificial bezoar and caffeine. Wherein, acetaminophen has antipyretic and analgesic effects by inhibiting prostaglandin synthesis, and can cause peripheral vasodilation, thereby inducing perspiration of organism to achieve antipyretic effect. In addition, it has peripheral analgesic effect. However, acetaminophen accounts for 90.6% of the total of 4 major components, which is hepatotoxic, and the rationality of acetaminophen drug use should be appreciated. Para-aminophenol is used as a starting material for the synthesis process of para-acetaminophen and may be carried into the final product due to incomplete acylation. The paracetamol has high toxicity, can cause skin mucosa irritation, has mutagenic and teratogenic effects, and can also cause acute poisoning. Therefore, there is a need to control the content of paracetamol in the compound paracetamol granules, and the current standard of the compound paracetamol granules is not marked with a method for detecting paracetamol impurities. Based on the reasons, the invention provides a method for detecting the paracetamol in the compound paracetamol granules, which ensures that the paracetamol is separated from the active ingredients or other unknown impurities efficiently and accurately and quantitatively, so that the paracetamol granules have good specificity, repeatability and accuracy, and can better ensure the safety and effectiveness of the medicament. Disclosure of Invention The invention aims to provide a method for detecting paracetamol in compound paracetamol and chlorphenamine maleate granules, which solves the problems, can detect related substances paracetamol by optimizing chromatographic conditions, improves the quality control technology of the compound paracetamol and chlorphenamine maleate granules, and further improves the medication safety of patients. In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: In one aspect, the invention provides a method for detecting paracetamol in compound paracetamol and chlorphenamine maleate granules, which is a high performance liquid chromatography method, and the chromatographic conditions are as follows: the chromatographic column is a nonpolar chromatographic column, and the filler is octadecylsilane chemically bonded silica gel; The flow rate is 0.9-1.1mL/min; Column temperature is 28-32 ℃; The detection wavelength is 255-259nm; Mobile phase: Mobile phase A is disodium hydrogen phosphate solution; Mobile phase B, methanol; solvent 15% methanol solution; the elution mode is gradient elution, and the gradient elution is as follows: 0-15min, 92% -88% of mobile phase A is changed to 75%, 8% -12% of mobile phase B is changed to 25%; 15-30min, 75% of mobile phase A is changed to 45%, and 25% of mobile phase B is changed to 55%; 30-44min, 45% of mobile phase A and 55% of mobile phase B; 44.1-55min, 92-88% of mobile phase A and 8-12% of mobile phase B. Preferably, the chromatographic column is Welch Xtimate ® C18 4.6X105 mm,5 μm or Thermo Acclaim TM C18.6X105 mm,5 μm, further preferably, the chromatographic column is Welch Xtimate ® C18.6X105 mm,5 μm. Preferably, the flow rate is 1.0ml/min. Preferably, the column temperature is 30 ℃. Preferably, the detection wavelength is 257nm. Preferably, the sample injection amount is 20 μl. Preferably, the concentration of the disodium hydrogen phosphate solution is 0.025mol/L. Preferably, the mobile phase A is disodium hydrogen phosphate solution with the pH of 6.6. Preferably, the disodium hydrogen p