HPLC法测定醋酸奥曲肽注射剂中乳酸对映异构体含量

目的：建立HPLC法和手性分离柱对醋酸奥曲肽注射剂中乳酸2种对映异构体进行拆分，并测定其含量，以评价产品的安全性。方法：采用手性柱Phenomenex Chirex 3126（D）-penicillami（4.6 mm×250 mm），流动相为2 mmol·L^-1硫酸铜溶液（溶剂为2%异丙醇溶液），流速为1.0 mL·min^-1，柱温35℃，紫外检测波长为230 nm。结果：L-乳酸与D-乳酸峰分离良好；L-乳酸浓度在0.51~3.05 mg·mL^-1范围内线性关系良好（r=1.000），平均回收率为100.9%（n=9）；D-乳酸浓度在4.19~41.90 μg·mL^-1范围内线性关系良好（r=0.999 7），平均回收率为99.8%（n=9）；70批醋酸奥曲肽注射液的L-乳酸含量在0.7~2.4 mg·mL^-1，D-乳酸含量在6.8~35.9 μg·mL^-1；21批注射用醋酸奥曲肽的L-乳酸含量在0.8~3.0 mg·mL^-1，D-乳酸含量在4.3~40.6 μg·mL^-1；诺华公司的1批醋酸奥曲肽注射液仅检出L-乳酸，含量为2.4 mg·mL^-1。结论：该方法操作简便、准确度高、灵敏度好，可用于醋酸奥曲肽注射剂中乳酸2种对映异构体的含量测定与质量控制。

Objective: To establish an HPLC method with a chiral column for enantiomeric separation of lactic acid, assay the content of each enantiomer and evaluate the safety in the octreotide acetate injection.Methods: A Phenomenex Chirex 3 126(D)-penicillami(4.6 mm×250 mm) chiral column was adopted.The detection wavelength was set at 230 nm. The mobile phase consisted of 2 mmol·L^-1 copper sulfate solution-isopropyl alcohol(98:2) at a flow rate of 1.0 mL·min^-1. The column temperature was set at 35℃.Results: L-lactic acid and D-lactic acid were well separated.The linear rang of L-lactic acid was 0.51 mg·mL^-1-3.05 mg·mL^-1(r=1.000), the average recovery was 100.9%(n=9).The linear rang of D-lactic acid was 4.19 μg·mL^-1-41.90 μg·mL^-1(r=0.999 7), the average recovery was 99.8%(n=9). The content range of L-lactic acid was 0.7-2.4 mg·mL^-1 and D-lactic acid was 6.8-35.9 μg·mL^-1 in 70 batches of octreotide acetate injection, the content range of L-lactic acid was 0.8-3.0 mg·mL^-1 and D-lactic acid was 4.3~40.6 μg·mL^-1 in 21 batches of octreotide acetate for injection.Only 2.4 mg·mL^-1 L-lactic acid was detected in original octreotide acetate injection from Novartis.Conclusion: The method is simple and easy to operate with high accuracy and sensitivity and which can be use for the determination of two lactic acid enantiomers and quality control in octreotide acetate injection and for injection.