Determination of penehyclidine by gas chromatographic-mass spectrometry and its application to pharmacokinetics in humans, rabbits and mice.
A sensitive and specific gas chromatographic-mass spectrometry with the extracted ion chromatograms (GC-MS/EIC) method has been developed and validated for the identification and quantification of penehyclidine (PH) in human and animal blood. The chromatography was on HP-5 capillary column (12 m x 0.2 mm x 0.3 microm). PH-d(5) was selected as the internal standard (IS). Simultaneous MS detection of PH and IS was performed at m/z 315 (PH) and m/z 320 (PH-d(5)), and the EIC of the two compounds was at 175 and 180. PH and PH-d(5) eluted at approximately 8.2 min and no endogenous materials interfered with their measurement. Linearity was obtained over the concentration range of 0.1-100 ng/ml in the blood. The lower limit of quantification (LLOQ) was reproducible at 50 pg/ml in both human and animal blood. The within-day and between-day precisions were no more than 9.1%. This method was successfully applied to quantification and pharmacokinetic studies of PH in the subjects. The concentration-time profiles of PH in humans, rabbits and mice were all fitted to first order absorption two-compartment open model after i.m. a single dose. The differences in absorption, distribution and elimination of PH among the species were found. The results provided the important information for developing a novel anti-cholinergic drug and for obtaining a more effectual remedy in clinical practice.
Xue
Ming
M
Beijing Institute of Pharmacology and Toxicology, 100850 Beijing, China. xuem@cpums.edu.cn
Yuan
Shulan
S
Ruan
Jinxiu
J
Qiao
Jianzhong
J
Xu
Yanxia
Y
Zhang
Zhenqin
Z
Liu
Keliang
K
D000328:Adult; D000818:Animals; D004355:Drug Stability; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D006801:Humans; D008297:Male; D051379:Mice; D011812:Quinuclidines / Q000097:blood / Q000493:pharmacokinetics*; D011817:Rabbits; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
D011812:Quinuclidines; C486140:penehyclidine