目的 建立UPLC-MS/MS测定比格犬血浆中的五味子醇甲血药浓度分析方法。方法 采用ACQUITY UPLC^® BEH C₁₈色谱柱（50 mm×2.1 mm，1.7 μm），流动相为0.1%乙酸水-甲醇梯度洗脱，体积流量为0.4 mL/min。柱温40℃，进样量5 μL。采用电喷雾（ESI）正离子模式进行多反应（MRM）监测，五味子醇甲和利伐沙班（内标）的定量离子对分别为m/z 433.20→384.30、437.19→145.13。结果 五味子醇甲在0.2～100 ng/mL线性关系良好（r=0.999 6），最低定量限为0.2 ng/mL，批内、批间精密度分别为2.04%～7.62%、3.72%～8.29%；基质效应及提取回收率分别为95.7%～103%、81.2%～106%；稳定性结果均符合生物样品检测指导原则。结论 建立的UPLC-MS/MS方法快速、简单、灵敏度高，能满足五味子醇甲血药浓度测定及其药动学研究。

Objective To establish UPLC-MS/MS method for determination of schisandrin in plasma of Beagle dogs. Methods The determination was carried out on ACQUITY UPLC^® BEH C₁₈ column (50 mm×2.1 mm, 1.7 μm). The mobile phase consisted of 0.1% acetic acid water-methanol with gradient elution at a flow rate of 0.4 mL/min. The column temperature was set at 40 ℃, and the injection volume was 5 μL. Electrospray positive ion mode was used for multi reaction monitoring, the quantitative ions of schisandrin and rivaroxaban (IS) were m/z 433.20→384.30 and 437.19→145.13, respectively. Results Schisandrin had good linearity in the ranges of 0.2 — 100 ng/mL (r=0.999 6). The minimum quantitative limit was 0.2 ng/mL, the intra and inter-day precision were 2.04% — 7.62% and 3.72% — 8.29%, respectively. The matrix effect and the recovery of extraction in the low, medium and high concentration were 95.7% — 103% and 81.2% — 106%, respectively. The results of stability accorded with the guiding principles of biological sample detection. Conclution The UPLC-MS/MS method is rapid, simple and sensitive, and can be used for the determination of schisandrin A in blood and its pharmacokinetics.

R969.1

国家科技重大专项（2015ZX09501004）