预灌封盐酸利多卡因注射剂质量检测方法及稳定性研究

Quality detection method and stability study of a prefilled syringe lidocaine hydrochloride injection

目的建立预灌封盐酸利多卡因注射剂中药物含量和有关物质的HPLC测定方法,进行方法学验证,并以所建方法考察预灌封盐酸利多卡因注射液的稳定性。方法参考2020版《中华人民共和国药典》,药物含量及有关物质测定均采用HPLC。药物含量测定采用Agilent Eclipse XDB-C_(18)色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-PBS(60∶40,体积比),流速为1 mL/min,进样量为20μL,检测波长为254 nm。药物有关物质测定除流动相乙腈-PBS(50∶50,体积比)、检测波长为230 nm不同以外,其他色谱条件与药物含量的测定方法一致。利用上述方法测定自制预灌封盐酸利多卡因注射剂中药物含量和有关物质,进行稳定性研究。结果含量测定方法在80.00~300.00μg/mL范围内线性关系良好(y=0.0343x+0.1627,r=0.9999),平均回收率为101.38%(相对标准偏差为0.39%,n=9)。杂质2,6-二甲基苯胺与盐酸利多卡因可良好分离,分离度>1.5,空白辅料不干扰测定,稳定性良好。结论建立的方法可用于预灌封盐酸利多卡因注射剂的含量及有关物质测定,方法简便、准确、灵敏度高、专属性强,为预灌封盐酸利多卡因注射剂的质量研究提供了定量分析方法,且不同稳定性试验条件下制剂质量稳定可靠。

Objective To establish and verify a high-performance liquid chromatography(HPLC)method for determining the content and related substances of a prefilled syringe lidocaine hydrochloride injection,and to carry out the stability study with this method.Methods Referring to the 2020 Chinese Pharmacopoeia,HPLC method was used to determine the drug content and related substances.The content of the drug was determined by Agilent Eclipse XDB-C_(18) column(4.6 mm×250 mm,5μm),the mobile phase was acetonitrile phosphate buffer(60∶40,volume ratio),the flow rate was 1.0 mL/min,the injection volume was 20μL,and the detection wavelength was 254 nm.For the determination of drugrelated substances,the chromatographic conditions were consistent with the determination of drug content,except that the mobile phase was acetonitrile-phosphate buffered saline(50∶50,volume ratio)and the detection wavelength was 230 nm.With the above HPLC method,the drug content and related substances in the prefilled syringe lidocaine hydrochloride injection were determined,and the injection stability was also studied.Results The linearity of the method was good in the range of 80.00-300.00μg/mL(y=0.0343x+0.1627,r=0.9999),with a mean recovery of 101.38%(relative standard deviation=0.39%,n=9).2,6-dimethylaniline,the related substances of lidocaine hydrochloride,could be well separated from lidocaine hydrochloride during the chromatographic separation.The resolution was greater than 1.5.The blank excipients did not interfere with the determination,and the stability was good.Conclusion The established method can be used for the determination of the content and related substances of the prefilled syringe lidocaine hydrochloride injection.It is simple,accurate,sensitive and specific,and provides a quantitative analysis method for the quality study of the prefilled syringe lidocaine hydrochloride injection.The preparation quality is stable and reliable under different conditions.