Zhong Ruijian, Yu Yan, Zheng Yangbing, Chen Weikang, Zhou Guoping, Ding Jianhong, Yuan Mingming
Jiangxi Institute for Drug Control, Nanchang, People's Republic of China.
School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, People's Republic of China.
Biomed Chromatogr. 2017 Aug;31(8). doi: 10.1002/bmc.3929. Epub 2017 Jan 25.
A simple, sensitive and specific UHPLC-MS/MS method for quantification of plantagoguanidinic acid (PGA) in rat plasma was applied to investigate the pharmacokinetic behavior in vivo, using protopine as internal standard. The chromatography was separated on a Phenomenex® Luna-C column (2.1 × 150 mm, 3.0 μm) within 7.0 min using a mobile phase consisting of acetonitrile-0.1% formic acid solution under gradient elution at a flow rate of 0.4 mL/min. Prepared samples were monitored by multiple reaction monitoring mode, with the target fragmentions m/z 226.2 → 84.2 for PGA and m/z 354.2 → 188.9 for IS in positive electrospray ionization. The calibration curve of PGA was linear throughout the range 1-1000 ng/mL (r = 0.9962). The lower limit of quantitation in plasma for PGA was 0.1 ng/mL, and the recovery was >88.6%. Intra- and interday accuracy ranged from -8.6 to 4.9%. Furthermore, this validated method was successfully used for a pre-clinical pharmacokinetic study of PGA at a single dose of 20 and 5 mg/kg in rats via oral and intravenous administration. The study showed that PGA was absorpted rapidly and eliminated gradually with a greater absolute oral bioavailability of 70.1% in rats.
采用一种简单、灵敏且特异的超高效液相色谱-串联质谱法（UHPLC-MS/MS），以普罗托品为内标，对大鼠血浆中的车前胍宁酸（PGA）进行定量，以研究其体内药代动力学行为。色谱分离采用Phenomenex® Luna-C柱（2.1×150 mm，3.0μm），在7.0分钟内完成，流动相为乙腈-0.1%甲酸溶液，梯度洗脱，流速为0.4 mL/min。制备的样品采用多反应监测模式进行监测，在正电喷雾电离中，PGA的目标碎片离子为m/z 226.2→84.2，内标的目标碎片离子为m/z 354.2→188.9。PGA的校准曲线在1-1000 ng/mL范围内呈线性（r = 0.9962）。PGA在血浆中的定量下限为0.1 ng/mL，回收率>88.6%。日内和日间精密度范围为-8.6%至4.9%。此外，该验证方法成功用于大鼠口服和静脉注射单剂量20和5 mg/kg的PGA的临床前药代动力学研究。研究表明，PGA吸收迅速，消除缓慢，在大鼠中的绝对口服生物利用度较高，为70.1%。
