[Identification of the metabolites of penehyclidine hydrochloride raceme in rats by LC-MS/MS and ion cluster].
OBJECTIVE
To study the metabolites of penehyclidine hydrochloride (PH) raceme, a new anticholinerigic drug invented by the Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences.


METHODS
Three healthy rat urine samples were collected within 24 h after a single i.m. dose of PH raceme and PH-d5 [(5 + 5) mg.kg-1] simultaneously. The eight metabolites of PH raceme were identified by the methods of LC-MS/MS, GC-MS, FAB-MS and the stable isotope ion cluster. Mass spectrometry was operated in the positive mode for the method of LC-MS/MS.


RESULTS
M1 and M1* were identified as the oxygenated products of PH in the cyclopentyl group; M2 and M2* were as the hydroxylated products of PH in the cyclopentyl group; M3 and M3* were as the oxygented and hydroxylated products of PH at the meta-position of cyclopentyl group; M4 and M4* were identified as the dihydroxylated metabolites of PH, the hydroxylated position were at the cyclopentyl group and quiniuclidinol ring of PH. Among them, M1 and M1*, M2 and M2*, M3 and M3*, M4 and M4* were the isomers of each other.


CONCLUSIONS
These characteristics can be used for future structure elucidation in studies of the metabolites of PH optical isomers. The structure data of PH metabolites provide important information for the clinical use and for developing better anticholinerigic drug.
Xue
Ming
M
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China. xurmd@163.net
Ruan
Jin-Xiu
JX
Yuan
Shu-lan
SL
Zhang
Zhen-qing
ZQ
Qiao
Jian-zhong
JZ
Guo
Ji-fen
JF
D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D008297:Male; D015394:Molecular Structure; D011812:Quinuclidines / Q000737:chemistry / Q000378:metabolism* / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
D002800:Cholinesterase Inhibitors; D011812:Quinuclidines; C486140:penehyclidine