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建立快速灵敏、简便的液相色谱-串联质谱(HPLC-MS/MS)法同时测定Wistar大鼠血浆中优格列汀及其代谢产物M1[(R)-8-(3-羟基哌啶-1-基)-7-(2-丁炔-1-基)-1-((5-氟苯并[d]噻唑-2-基)甲基)-3-甲基-1H-嘌呤-2,6(3H,7H)-二酮],并研究优格列汀、M1在Wistar大鼠体内的药代动力学特征。优格列汀、M1分别以利格列汀和地塞米松为内标,血浆样品经乙腈沉淀蛋白后,以10%乙腈水溶液(含4 mmol·L-1醋酸铵,0.1%甲酸)-90%甲醇水溶液(含4 mmol·L-1醋酸铵,0.1%甲酸)为流动相,通过Grace Altima HP C18柱(2.1 mm×50 mm,5μm)梯度洗脱,色谱运行时间为4.4 min。采用电喷雾电离源,以多反应监测方式进行正离子检测。优格列汀、M1的标准曲线的线性范围均为0.5~500 ng·mL-1,定量下限均为0.5 ng·mL-1,日内和日间精密度(RSD)均小于14%。应用此法研究了Wistar大鼠口服灌胃给予优格列汀混悬液(27 mg·kg-1)后的药动学特点。本方法简便、准确、专属性强,适用于优格列汀和M1在Wistar大鼠体内的药代动力学研究。
To establish a rapid and sensitive HPLC-MS / MS method for the simultaneous determination of yogurtley and its metabolite M1 [(R) -8- (3-hydroxypiperidine- (5-fluorobenzo [d] thiazol-2-yl) methyl) -3- methyl-1 H -purin-2-yl) -7- , 6 (3H, 7H) -dione], and studied the pharmacokinetics of yogurting and M1 in Wistar rats. The plasma samples were precipitated with acetonitrile and treated with 10% acetonitrile in water (containing 4 mmol·L -1 ammonium acetate, 0.1% formic acid) -90 % Methanol aqueous solution containing 4 mmol·L -1 ammonium acetate and 0.1% formic acid as mobile phase, and the chromatographic run time was 4.4 min on a Grace Altima HP C18 column (2.1 mm × 50 mm, 5 μm). Electrospray ionization source is used for positive ion detection with multiple reaction monitoring methods. The linear range of the standard curve of yolkliptin and M1 was 0.5-500 ng · mL-1, and the lower limit of quantification was 0.5 ng · mL-1. The RSDs were both less than 14%. This method was used to study the pharmacokinetics of wistar rats after oral gavage of yogurtley (27 mg · kg-1). The method is simple, accurate and specific, and is suitable for the pharmacokinetics study of voglossin and M1 in Wistar rats.