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目的建立LC-MS/MS法同时测定人血浆中辛伐他汀及其活性代谢物辛伐他汀酸的质量浓度,用于评价辛伐他汀片受试制剂和参比制剂的生物等效性。方法血浆样品经液-液萃取后,采用SHISEIDO CAPCELL PAK C18MGⅡ(50 mm×2.0 mm,5μm I.D)色谱柱,流动相A为水(含体积分数为0.5‰的甲酸),流动相B为甲醇-乙腈(体积比为7∶3,含体积分数为0.5‰的甲酸)。质谱采用多反应离子监测模式(MRM),以正离子电离模式测定。结果辛伐他汀和辛伐他汀酸的线性范围分别为质量浓度0.205 0~20.50μg·L-1和质量浓度0.201 0~20.10μg·L-1;辛伐他汀和辛伐他汀酸最低定量限分别为质量浓度0.205 0μg·L-1和0.201 0μg·L-1。日内、日间精密度RSD均小于8.32%,准确度为97.12%~107.46%,提取回收率为74.98%~93.98%。2种制剂的相对生物利用度都接近100%。结论本方法快速、灵敏、专属性强,适用于同时测定人血浆中辛伐他汀和辛伐他汀酸,并可以应用于辛伐他汀片的生物等效性研究评价。
OBJECTIVE To establish a simultaneous LC-MS / MS method for simultaneous determination of simvastatin and its active metabolite simvastatin acid in human plasma for evaluating the bioequivalence of simvastatin tablets and reference preparations. Methods The plasma samples were separated on a SHISEIDO CAPCELL PAK C18MG Ⅱ (50 mm × 2.0 mm, 5 μm ID) column using liquid-liquid extraction. The mobile phase A was water (containing 0.5 ‰ of formic acid) and the mobile phase B was methanol- Acetonitrile (7: 3 by volume, 0.5% by volume formic acid). Mass spectrometry using multiple reaction ion monitoring mode (MRM), measured in positive ionization mode. Results The linear range of simvastatin and simvastatin acid were 0.205 0 ~ 20.50 μg · L-1 and 0.201 0 ~ 20.10 μg · L-1, respectively. The minimum limit of quantification of simvastatin and simvastatin was The concentrations of 0.205 0μg · L-1 and 0.201 0μg · L-1. The intra-day and inter-day precision RSD were less than 8.32%, the accuracy was 97.12% ~ 107.46%, the extraction recovery was 74.98% ~ 93.98%. The relative bioavailability of both formulations was close to 100%. Conclusion The method is rapid, sensitive and specific. It is suitable for the simultaneous determination of simvastatin and simvastatin acid in human plasma and can be used in the bioequivalence assessment of simvastatin tablets.