School of Pharmacy, China Medical University, Shenyang, 110122, PR China.
School of Pharmacy, China Medical University, Shenyang, 110122, PR China.
J Pharm Biomed Anal. 2019 May 30;169:208-214. doi: 10.1016/j.jpba.2019.03.012. Epub 2019 Mar 6.
As a novel alkaloid, trolline is a potential methionine aminopeptidase Ⅱ inhibitor. However, up to now, no informations about the quantification of trolline were available in biosamples. In this study, a simple, specific and sensitive analytical method based on UHPLC-MS/MS method has been established and validated for determination of trolline in rat plasma and tissues after intravenous administration. Sample preparation was carried out by a simple liquid-liquid extraction and carbamazepine was used as internal standard (I.S.). Chromatographic separation was achieved by using a Waters BEH C column and involving the optimized mobile phase of 0.1% formic acid aqueous solution and acetonitrile with gradient elution flow of 0.20 ml/min. Trolline and I.S. were detected by multiple reaction monitoring (MRM) modes with positive electrospray ionization and transitions at m/z 220.0→136.8 for trolline and m/z 237.0→193.9 for carbamazepine (I.S.). Good linearity was ranged from 10.0 ng/ml to 4000 ng/ml for trolline both in plasma and various tissues. The lower limit of quantification (LLOQ) was 10 ng/ml in all samples. The intra- and inter-day precision (RSD%) were below 11.3% and the accuracy (RE%) was ranged from -10.2% to 12.3%. The validated method was successfully applied to the pharmacokinetics and tissue distribution study of trolline after intravenous administration.
作为一种新型生物碱，trolline 是潜在的蛋氨酸氨肽酶 2 抑制剂。然而，到目前为止，生物样本中还没有关于 trolline 定量的信息。在本研究中，建立并验证了一种基于 UHPLC-MS/MS 法的简单、特异和灵敏的分析方法，用于测定大鼠静脉给药后血浆和组织中的 trolline。样品制备采用简单的液-液萃取法，卡马西平作为内标（IS）。色谱分离采用 Waters BEH C 柱，优化的流动相为 0.1%甲酸水溶液和乙腈，梯度洗脱流速为 0.20ml/min。Trolline 和 IS 通过正电喷雾电离，以多反应监测（MRM）模式检测，trolline 的监测离子对为 m/z 220.0→136.8，IS 的监测离子对为 m/z 237.0→193.9。Trolline 在血浆和各种组织中的线性范围均为 10.0ng/ml 至 4000ng/ml。所有样品的定量下限（LLOQ）均为 10ng/ml。日内和日间精密度（RSD%）均低于 11.3%，准确度（RE%）在-10.2%至 12.3%之间。该验证方法成功应用于静脉给药后 trolline 的药代动力学和组织分布研究。
