College of Pharmaceutical Engineering of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China; State key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, PR China.
Hunan Zhengqing Pharmaceutical Group Co., Ltd, Huaihua 418005, PR China.
J Pharm Biomed Anal. 2022 Sep 20;219:114970. doi: 10.1016/j.jpba.2022.114970. Epub 2022 Jul 27.
Zhengqing Fengtongning injection is the sterile aqueous solution of Sinomenine Hydrochloride extracted from the root and stem of Sinomenium acutum, and is widely used to treat rheumatoid arthritis. Due to the processes of extraction, separation, purification, preparation and storage, some related impurities might be formed, which may cause side effects on patients. It is important to rapidly separate and identify the related impurities to ensure the safe use of Zhengqing Fengtongning injection. However, there are few literatures about the impurity in Zhengqing Fengtongning injection. In this work, ultra-high performance liquid chromatography- quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS) was developed to analyze impurities in both Zhengqing Fengtongning injection and its drug substance, with Sinomenine Hydrochloride as its active pharmaceutical ingredient (API). Six impurities of the Zhengqing Fengtongning injection were found. Structures of impurities 1 and 6 were confirmed by NMR and other impurities were identified from the fragmentation pattern of Sinomenine, the similarity of molecular weight and fragment ions in references. Finally, the HPLC analytical technique was developed to achieve the quantification of impurities 1 and 6. In addition, some reasonable suggestions are put forward on the quality control of Zhengqing Fengtongning injection and its drug substance based on the processes and structural characteristics of the related substances. The technical system established in this paper is helpful to strengthen the quality control of Zhengqing Fengtongning injection and improve production, and can also provide references for the production and quality control of similar drugs.
正清风痛宁注射液是从青风藤的根和茎中提取的盐酸青藤碱的无菌水溶液，广泛用于治疗类风湿关节炎。由于提取、分离、纯化、制备和储存过程，可能会形成一些相关的杂质，这可能会对患者产生副作用。快速分离和鉴定相关杂质对于确保正清风痛宁注射液的安全使用非常重要。然而，关于正清风痛宁注射液中的杂质的文献很少。在这项工作中，采用超高效液相色谱-四极杆飞行时间质谱（UPLC-QTOF/MS）分析了正清风痛宁注射液及其药物成分盐酸青藤碱中的杂质，以盐酸青藤碱为活性药物成分（API）。发现正清风痛宁注射液中有 6 种杂质。杂质 1 和 6 的结构通过 NMR 确定，其他杂质则根据青藤碱的碎片模式、分子量和碎片离子在参考文献中的相似性进行了鉴定。最后，建立了 HPLC 分析技术，实现了杂质 1 和 6 的定量分析。此外，还根据相关物质的工艺和结构特点，对正清风痛宁注射液及其药物成分的质量控制提出了一些合理的建议。本文建立的技术体系有助于加强正清风痛宁注射液的质量控制，提高生产水平，也可为类似药物的生产和质量控制提供参考。
