天麻素注射液的杂质谱研究

目的：研究天麻素注射液的杂质谱，采用高效液相色谱-三重四极杆线性离子肼质谱（Q-TRAP LC/MS/MS）联用技术鉴定杂质的结构，并归属杂质来源，明确杂质与生产及储存的关系。方法：采用HPLC法测定18家企业的200批天麻素注射液的有关物质，确定检出杂质，同时对天麻素进行强制降解试验研究，归属杂质来源，并采用Q-TRAP LC/MS/MS及HPLC对照比对法鉴定杂质结构。结果：天麻素注射液中共检测到3种杂质：4-醛基苯基-β-D-吡喃葡萄糖苷（杂质1）、对羟基苯甲醇（杂质2）和4-羟甲基苯基-二元糖苷（杂质3）。其中杂质1为合成工艺杂质也是氧化降解杂质，检出量最大，在所有制剂的样品及原料药样品中均检出，其校正因子为1.04；杂质2为酸碱降解杂质，在部分样品中检出；杂质3为一种原料药生产工艺的特有杂质，在该工艺的原料药及部分制剂的样品中检出。结论：本研究基于质量源于设计理念，对天麻素注射液的杂质进行了结构鉴定及来源归属，为其工艺优化，提高产品质量及质量控制提供参考。

Objective: To investigate the impurity profile of gastrodin injection, identify the structures of impurities by triple quadrupole-linear ion trap mass spectrometry(Q-TRAP LC/MS/MS), and investigate the relations between impurities and production & storage. Methods: The related substances in 200 batches of gastrodin injection from 18 companies were determined by HPLC to confirm the impurities. The sources of impurities were studied by degradation test. The structures of impurities were identified by Q-TRAP LC/MS/MS and HPLC comparison test. Results: Three impurities were identified as 4-formylpheny-β-D-glucopyranosid(impurity 1), 4-hydroxybenzyl alcohol(impurity 2)and 4-hydroxymethylpheny-l-binary indicant(impurity 3). The impurity 1, which was found as the impurity with the highest content in all injection samples and two pharmaceutical ingredient(API)samples, was identified as by-product and degradation product. Its correction factor was 1. 04. The impurity 2, which was found in some injection samples, was identified as hydrolyzing degradation product. The impurity 3, which was found in one API and some injection samples, was identified as a specific by- product of from that API process.Conclusion: Based on theory of quality by design(QbD), the structures and sources of impurities in gastrodin injection were identified, thus providing reference for optimizing synthesis process, improving the quality of products and quality control.