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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×250mm),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 m L·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·m L~(-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4.19~41.90μg·m L~(-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·m L~(-1),D-乳酸含量在6.8~35.9μg·m L~(-1);21批注射用醋酸奥曲肽的L-乳酸含量在0.8~3.0 mg·m L~(-1),D-乳酸含量在4.3~40.6μg·m L~(-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·m L~(-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 and a chiral separation column for the separation of two enantiomers of lactic acid in octreotide acetate injection and determine the content of lactic acid in order to evaluate the safety of the product. Methods: The mobile phase consisted of 2 mmol·L -1 copper sulfate solution (2% isopropanol solvent) with a mobile phase of Phenomenex Chirex 3126 (D) -penicillami (4.6 mm × 250 mm) m L · min ~ (-1). The column temperature was 35 ℃ and UV detection wavelength was 230 nm. Results: The separation of L-lactic acid and D-lactate peak was good. L-lactic acid had a good linearity (r = 1.000) within the range of 0.51-3.05 mg · m L -1 with an average recovery of 100.9% (n = 9). The linearity of D-lactate ranged from 4.19 to 41.90 μg · m L -1 (r = 0.999 7) and the average recovery was 99.8% (n = 9). Seventy batches of octreotide acetate injection L-lactic acid content of 0.7-2.4 mg · m L -1, D-lactic acid content of 6.8-35.9 μg · m L -1. The content of L-lactic acid in 21 batches of octreotide acetate for injection was 0.8 ~ 3.0 mg · m L -1, D-lactic acid content was 4.3 ~ 40.6 μg · m L -1; only Novartis’s first batch of octreotide acetate injection detected only L- · M L -1 (-1). Conclusion: The method is simple, accurate, and sensitive. It can be used for the determination and quality control of two enantiomers of lactic acid in octreotide acetate injection.