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目的:建立LC-MS/MS法测定卡巴他赛在比格犬血浆中的浓度,并将该方法应用于卡巴他赛注射液在比格犬体内的药动学研究。方法:以卡马西平为内标,血浆样品经甲醇沉淀蛋白,富集生物样品中的卡巴他赛,然后进行LC-MS/MS检测。色谱柱采用Agilent EC C_(18)柱(50 mm×4.6 mm,2.7μm),柱温为30℃,以甲醇-水(95∶5)为流动相,流速为0.5 ml·min~(-1),进样量为5μl,采用电喷雾电离源(ESI),正离子多反应监测(MRM)扫描分析,卡巴他赛和内标的离子选择通道分别为m/z858.4→577.4,m/z 237.1→194.1;比格犬单剂量静脉静滴卡巴他赛注射液20 mg·h~(-1),于不同时间点取血测定血浆中药物的含量并利用DAS 2.0软件计算其药动学参数。结果:卡巴他赛在10.0~1 000.0 ng·ml~(-1)范围内线性关系良好,平均回收率均大于93.53%,日内与日间精密度(RSD)均小于7.4%。比格犬静脉注射卡巴他赛后AUC(0-t)为(155 181.93±11 593.33)ng·ml~(-1)·min~(-1),AUC(0-∞)为(167 528.12±16 671.46)ng·ml~(-1)·min~(-1),t_(max)为60 min,C_(max)为(688.37±52.06)ng·ml~(-1)。结论:该法快速、精确、简便,可用于比格犬血浆中卡巴他赛的测定及药动学研究。
OBJECTIVE: To establish a LC-MS / MS method for the determination of concentration of cabazitaxel in Beagle dogs plasma. The method was applied to the pharmacokinetics of cabazitaxel in Beagle dogs. Methods: Carbamazepine was used as an internal standard. Plasma samples were precipitated with methanol and enriched in cabazitaxel in biological samples. LC-MS / MS was used to detect the content of carbamazepine. The column was equipped with an Agilent EC C 18 column (50 mm × 4.6 mm, 2.7 μm) with a column temperature of 30 ° C and a mobile phase of methanol-water (95: 5) at a flow rate of 0.5 ml · min -1 ), And the injection volume was 5μl. The electrospray ionization source (ESI) and positive ion MRM (multi-reaction monitoring) scanning analysis were used. The ion channel of cabazitaxel and the internal standard was m / z858.4 → 577.4, m / z 237.1 → 194.1; beagle dogs single intravenous infusion of cabazitaxel injection of 20 mg · h ~ (-1), at different time points blood samples were taken for determination of plasma drug content and the use of DAS 2.0 software to calculate the pharmacokinetic parameters . Results: Cabazitaxel had a good linearity in the range of 10.0-1 000.0 ng · ml -1 with an average recovery of more than 93.53%. The intra-and inter-day RSD was less than 7.4%. The AUC (0-t) was (181.93 ± 11 593.33) ng · ml -1 · min -1 and the AUC (0-∞) was (167 528.12 ± 16 671.46 ng · ml -1 · min -1, t max 60 min and C max 688.37 ± 52.06 ng · ml -1. Conclusion: The method is rapid, accurate and simple and can be used for the determination and pharmacokinetics of cabazitaxel in beagle dogs plasma.