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HPLC detection method for propranolol hydrochloride genotoxic impurities

A technology of propranolol hydrochloride gene and propranolol hydrochloride, applied in the field of HPLC detection of propranolol hydrochloride genotoxic impurities, can solve the problems of unfavorable quality control of propranolol hydrochloride tablets, poor solubility of genotoxic impurities, etc. , to meet the requirements of qualitative and quantitative detection, suitable chromatographic conditions, and good durability

Active Publication Date: 2020-11-13
JIANGSU YUNYANG PHARMA GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Propranolol hydrochloride API has good solubility in water, and genotoxic impurities have poor solubility in water. 1-Naphthol is colorless or yellow, has a phenol smell, crystal or powder, and becomes rose-colored when exposed to light. Naphthalene glycidol Ether is a colorless to pale yellow liquid. At present, there is no effective analytical method for the detection of 1-naphthol and naphthalene glycidyl ether genotoxic impurities in propranolol hydrochloride, which is not conducive to propranolol hydrochloride tablets. quality control of

Method used

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  • HPLC detection method for propranolol hydrochloride genotoxic impurities
  • HPLC detection method for propranolol hydrochloride genotoxic impurities
  • HPLC detection method for propranolol hydrochloride genotoxic impurities

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Experimental program
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Effect test

Embodiment 1-5

[0021] (1) Reagent selection: acetonitrile: Merck, batch number: SBK5734; phosphoric acid: Sinopharm, batch number: 20170929.

[0022] (2) Sample selection: Propranolol hydrochloride (API) provided by Yunyang (batch number 180101, 170201, 170202); 1-naphthol: Aladdin, batch number: K1717022; naphthalene glycidyl ether: LGC, batch number: 43050702, content 99.6%; Impurity A: LGC, lot number: 43010801; Impurity B: LGC, lot number: 79125; Impurity C: LGC, lot number: 66021.

Embodiment 1-4

[0024] Solution preparation: 1-naphthol and glycidyl ether are classified as Type 2 impurities by ICHM7. The maximum daily dose of propranolol hydrochloride is 240mg. The impurity limit is calculated according to the TTC method, 1.5μg / day÷240mg / day=6.25ppm, Check the quality standards of propranolol hydrochloride in various national pharmacopoeias. Only the Chinese Pharmacopoeia stipulates that 1-naphthol must not exceed 300ppm. JP17, USP41, and EP9.0 do not stipulate the limits of 1-naphthol and naphthalene glycidyl ether. According to the requirements of current regulations and Strict control strategy, the limit of 1-naphthol and glycidyl ether is proposed to be 6.25ppm, in order to make the impurity in the API controllable within 6.25ppm, the API concentration is 50mg / ml, and the impurity limit concentration is 0.3125μg / ml for analysis method development.

[0025] Diluent: The diluent consists of acetonitrile and water in a volume ratio of 1:1;

[0026] Mix the reference s...

Embodiment 1

[0031] The above-mentioned system suitability solution is detected by 106 Agilent VWD high-performance liquid chromatography instruments, and the conditions of high-performance liquid chromatography are: C18 chromatographic column; with phosphoric acid aqueous solution as mobile phase A, the volume percentage of phosphoric acid in mobile phase A phosphoric acid aqueous solution is 0.1 %, with acetonitrile as mobile phase B, gradient elution was performed, the flow rate was 1.0ml / min, the injection volume was 40μl, and the column temperature was 30°C;

[0032] The chromatographic column adopts octadecylsilane bonded silica gel as filler Waters Atlantis T3 (4.6 × 150mm, 3 μ m) chromatographic column, and the gradient elution program is: time 0min: mobile phase B is 40%, time 18min flow Phase B is 40%, time 25min mobile phase B is 50%, time 35min mobile phase B is 50%, time 36min mobile phase B is 80%, time 45min mobile phase B is 80%, time 46min mobile phase B is 40% , time 55mi...

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Abstract

The invention relates to an HPLC (High Performance Liquid Chromatography) detection method for propranolol hydrochloride genotoxic impurities. The method comprises the following steps of: preparing amixed reference substance mother solution from 1-naphthol, naphthyl glycidyl ether and a diluent in a constant-volume manner; preparing a sample solution from propranolol hydrochloride and a diluent in a constant-volume mode; and detecting the mixed reference substance mother solution and the sample solution by adopting a high performance liquid chromatograph to obtain a qualitative and quantitative detection result of propranolol hydrochloride genotoxic impurities 1-naphthol and naphthyl glycidyl ether, wherein the conditions of high performance liquid chromatography as follows: a C18 chromatographic column is adopted; and gradient elution is carried out by taking a phosphoric acid aqueous solution as a mobile phase A and acetonitrile as a mobile phase B at the column temperature of 20-30DEG C and the detection wavelength of 215-220nm. The method has the advantages of good specificity, solution stability, sensitivity, linearity, accuracy, precision and durability, appropriate chromatographic conditions and good separation effect, can meet the requirements of qualitative and quantitative detection, and is beneficial to quality control of genotoxic impurities 1-naphthol and naphthyl glycidyl ether in API so as to monitor the quality of drugs.

Description

technical field [0001] The invention relates to an HPLC detection method for propranolol hydrochloride genotoxic impurities, belonging to the technical field of propranolol hydrochloride detection methods. Background technique [0002] Propranolol hydrochloride is a β-receptor blocking drug, which blocks the β receptors of the myocardium, slows down the heart rate, inhibits cardiac contractility and conduction, reduces circulating blood volume, and reduces myocardial oxygen consumption. It is mainly used clinically for the treatment of Arrhythmia caused by many reasons can also be used for angina pectoris, hypertension, pheochromocytoma, etc. Consistency evaluation of propranolol hydrochloride tablets requires research on the quality of the API and the genotoxic impurity 1-naphthol in the API starting material and naphthalene glycidyl ether For quality control, these two genotoxic impurities are classified as Type 2 impurities by ICHM7, and the quality standards of propr...

Claims

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Application Information

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IPC IPC(8): G01N30/02
CPCG01N30/02
Inventor 王国华董少华岳明邹翔
Owner JIANGSU YUNYANG PHARMA GRP
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