CN-121978234-A - Method for detecting polymer in lipoic acid injection

Abstract

The invention provides a method for detecting polymer in lipoic acid injection, which adopts a liquid chromatography-mass spectrometry combined detection method to carry out qualitative detection analysis on polymer impurities in lipoic acid injection, adopts high performance liquid chromatography to carry out quantitative detection analysis and nuclear magnetism quantitative confirmation on the polymer impurities, can separate and quantitatively measure polymer impurities in lipoic acid injection containing lipoic acid and at least seven common impurities in the high performance liquid chromatography, has high accuracy, good specificity, high analysis speed, stable linear relation and good reproducibility, is convenient for qualitative and quantitative quality detection and monitoring of lipoic acid injection, ensures the quality stability and safety of lipoic acid injection, and is favorable for popularization and application.

Inventors

• MIAO YAN
• WANG HUIMIN
• GAO HUILI
• LIANG ZHISHOU

Assignees

• 江苏睿实生物科技有限公司

Dates

Publication Date

20260505

Application Date

20251231

Claims (10)

1. 1. A method for detecting polymer in lipoic acid injection is characterized in that a liquid chromatography-mass spectrometry combined detection method is adopted to carry out qualitative detection analysis on polymer impurities in lipoic acid injection, and high performance liquid chromatography is adopted to carry out quantitative detection analysis and nuclear magnetism quantitative confirmation on the polymer impurities.
2. 2. The method for detecting polymer in lipoic acid injection according to claim 1, wherein the method is characterized in that a dual quadrupole mass spectrometer LC-MS is adopted to detect and analyze the polymerization mode and molecular weight of the polymer in the lipoic acid injection.
3. 3. The method for detecting the polymer in the lipoic acid injection according to claim 2, wherein the dual quaternary rod mass spectrometer is Shimadzu LCMS-MS-8040 dual quaternary rod mass spectrometer, and the chromatographic column is a C18 chromatographic separation column using octadecylsilane chemically bonded silica gel as a filler.
4. 4. The method for detecting the polymer in the lipoic acid injection according to claim 3, wherein the particle size of the chromatographic column filler is 2.5-4.5 μm.
5. 5. The method for detecting polymer in lipoic acid injection of claim 3, wherein formic acid solution is used as mobile phase A, and a mixture of methanol, acetonitrile and tetrahydrofuran is used as mobile phase B.
6. 6. The method for detecting polymer in lipoic acid injection of claim 5, wherein the concentration of the formic acid solution is 0.05% -0.15%.
7. 7. The method for detecting the polymer in the lipoic acid injection according to any one of claims 3 to 6, which is characterized in that gradient elution is carried out under the chromatographic condition at the flow rate of 1.0 ml/min+/-0.1 ml/min, the column temperature of 35 ℃ +/-2 ℃ and the initial ratio of mobile phases of 95:5 to 85:15.
8. 8. The method for detecting polymer in lipoic acid injection of claim 7, wherein the gradient change of gradient elution is: 。
9. 9. the method for detecting polymer in lipoic acid injection as claimed in claim 1, wherein the high performance liquid chromatograph is Agilent 1260, and the chromatographic column is C18 chromatographic separation column using octadecylsilane chemically bonded silica as filler.
10. 10. The method for detecting the polymer in the lipoic acid injection according to claim 9, wherein the particle size of the chromatographic column filler is 2.5-4.5 μm, and gradient elution is carried out under the chromatographic conditions of the flow rate of 1.0ml/min +/-0.1 ml/min, the column temperature of 35 ℃ +/-2 ℃ and the initial mobile phase ratio of 95:5-85:15.

Description

Method for detecting polymer in lipoic acid injection Technical Field The invention relates to the technical field of drug analysis and test and drug quality control, in particular to a method for detecting a polymer in lipoic acid injection. Background With changes in eating habits and lifestyle of people, the incidence of diabetes mellitus has been gradually increased in recent years. Lipoic acid (Alpha Lipoic Acid) is coenzyme existing in mitochondria, has high free radical reaction capability, can eliminate free radicals in vivo, and has the effects of diminishing inflammation and resisting aging. Is widely used for preventing and treating heart diseases, diabetes, liver diseases and senile dementia at present. According to statistics, about 1.5-2 hundred million diabetics exist in the world, and nearly 1 hundred million diabetics exist in China, so that the life quality of people is seriously affected. Diabetic peripheral neuropathy (diabetic peripheral neuropathy, abbreviated DPN) is a common complication of diabetes mellitus and its pathogenesis is irreversible, and is a high risk factor for causing diabetic foot, infection. Lipoic acid can inhibit lipid oxidation of nerve tissue, prevent protein glycosylation, inhibit aldose reductase, and prevent glucose or galactose from generating sorbitol. Toxicology experiments show that the medicine can prevent diabetes from developing, promote glucose utilization and prevent neuropathy caused by hyperglycemia. The lipoic acid injection is unstable, polymer impurities are easy to generate, the polymer state is complex, the polymer control method carried by European pharmacopoeia is a thin layer chromatography, belongs to semi-quantitative detection and control methods, and cannot accurately quantify each polymer impurity, in addition, according to the detection methods of the polymer impurities in some lipoic acid medicaments which are already disclosed, a plurality of polymers in the lipoic acid medicament preparation and impurity peaks of a plurality of polymers can be qualitatively identified, and the detection control method only performs qualitative analysis on the polymers, and does not give out quantitative analysis and test methods. The lipoic acid injection is liquid preparation, polymer impurities are easy to produce, and the polymer impurities affect the safety of the preparation, so that a detection control method capable of accurately and qualitatively and quantitatively controlling the polymer impurities in the preparation is needed. Disclosure of Invention The invention aims to overcome the defects of the prior art and provides a method for detecting polymers in lipoic acid injection, wherein the qualitative analysis is carried out on each polymer impurity in lipoic acid injection samples, and the quantitative analysis and control are carried out on the impurities by using the detection method to carry out the external standard method of main components. In order to achieve the above purpose, the invention provides a method for detecting a polymer in a lipoic acid injection, which adopts a liquid chromatography-mass spectrometry combined detection method to carry out qualitative detection analysis on polymer impurities in the lipoic acid injection, and adopts high performance liquid chromatography to carry out quantitative detection analysis and nuclear magnetism quantitative confirmation on the polymer impurities, thereby effectively controlling the content of the polymer impurities in the lipoic acid injection. Further, detecting and analyzing the polymerization mode and the molecular weight of the polymer in the lipoic acid injection by adopting a double quadrupole mass spectrometer LC-MS; The dual quaternary rod mass spectrometer is an Shimadzu LCMS-MS-8040 dual quaternary rod mass spectrometer, wherein the chromatographic column is a C18 chromatographic separation column using octadecylsilane chemically bonded silica as a filler, and the filler particle size of the chromatographic column is 2.5-4.5 mu m; Preferably, the column is Waters XSelect CSH TM C18 (4.6 mm. Times.150 mm, particle size 3.5 μm). Preferably, formic acid solution is used as a mobile phase A, and a mixture of methanol, acetonitrile and tetrahydrofuran is used as a mobile phase B; Preferably, the concentration of the formic acid solution is 0.05% -0.15%, the concentration of the formic acid solution is 0.1%, and the ratio of the methanol to the acetonitrile to the tetrahydrofuran is (500:400:100) and is a mobile phase B; further, chromatographic conditions were at a flow rate (1.0 ml/min.+ -. 0.1 ml/min), column temperature (35 ℃.+ -. 2 ℃), mobile phase starting ratio (95:5/85:15); preferably, the flow rate is 1ml/min per minute, the column temperature is 35 ℃, the temperature of a sample injection chamber is 6 ℃, the detection wavelength is 241nm, the sample injection volume is 40 μl, and gradient change elution is carried out (a trapping column is arranged between a grad