Liu Mei, Su Xianying, Li Guofei, Zhao Guilian, Zhao Limei
Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, China.
Northeast Pharmaceutical (Shenyang) Science & Technology Development Co., Ltd., Shenyang, China.
J Chromatogr B Analyt Technol Biomed Life Sci. 2015 Dec 1;1006:8-15. doi: 10.1016/j.jchromb.2015.09.033. Epub 2015 Oct 19.
A rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method was developed and validated for simultaneous quantification of simvastatin (SV), its metabolite simvastatin hydroxy acid (SVA) and berberine (BBR) in rat plasma. Separation was performed on Poroshell 120 EC-C18 column (4.6×50mm, 2.7μm) using gradient elution by mobile phase containing acetonitrile and 10mM ammonium acetate (pH 4.5). Polarity switch (positive-negative-positive ionization mode) was performed in a total run time of 4.0min. The lower limits of quantification (LLOQ) for SV, SVA and BBR were 0.10, 0.20 and 0.10ng/mL, respectively. The response function was established for concentration range of 0.10-100ng/mL for SV and BBR and 0.20-3000ng/mL for SVA, with a coefficient of correlation of >0.99 for all the compounds. The proposed method was applied to the drug-drug pharmacokinetic interaction study of SV combined with BBR after oral administration in rats.
建立并验证了一种快速灵敏的液相色谱-串联质谱（LC-MS/MS）分析方法，用于同时定量大鼠血浆中辛伐他汀（SV）、其代谢产物辛伐他汀羟基酸（SVA）和小檗碱（BBR）。采用Poroshell 120 EC-C18柱（4.6×50mm，2.7μm），以含乙腈和10mM醋酸铵（pH 4.5）的流动相进行梯度洗脱分离。在4.0分钟的总运行时间内进行极性切换（正-负-正电离模式）。SV、SVA和BBR的定量下限（LLOQ）分别为0.10、0.20和0.10ng/mL。建立了SV和BBR在0.10-100ng/mL浓度范围以及SVA在0.20-3000ng/mL浓度范围的响应函数，所有化合物的相关系数均>0.99。该方法应用于大鼠口服给药后SV与BBR的药物-药物药代动力学相互作用研究。
