Determination of solifenacin succinate, a novel muscarinic receptor antagonist, and its major metabolite in rat plasma by semi-micro high performance liquid chromatography.
A sensitive and specific method for the simultaneous determination of the unchanged drug (solifenacin) and its major metabolite (M1, 4S-hydroxy solifenacin) in rat plasma was developed and validated. Both solifenacin and M1 were extracted from rat plasma by a two-step liquid-liquid extraction and analyzed by semi-micro HPLC with UV detection at an absorbance wavelength of 220 nm. The chromatographic separations were performed on a TSKgel ODS-80Ts (5 microm, 150 mmx2.0 mm i.d.) reversed-phase column with a mobile phase of 0.1 M phosphate buffer (pH 3.0):acetonitrile (71:29, v/v). The intra-day precision (expressed as coefficient of variation, CV) ranged from 0.4% to 1.7%, and the accuracy (expressed as relative error, RE) ranged from -5.2% to 2.0% for solifenacin. The corresponding precision ranged from 1.3% to 3.2%, and accuracy ranged from -4.0% to 8.6% for M1. The lower limit of quantitation for both solifenacin and M1 was 2 ng/ml when 1 ml of plasma was used. No endogenous interference was observed in rat plasma.
Yanagihara
Takamitsu
T
Drug Metabolism Research Laboratories, Astellas Pharma Inc., 1-8, Azusawa 1-chome, Itabashi-ku, Tokyo 174-8511, Japan. takamitsu.yanagihara@jp.astellas.com
Aoki
Toshiko
T
Soeishi
Yoshiaki
Y
Iwatsubo
Takafumi
T
Kamimura
Hidetaka
H
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D008297:Male; D008832:Microchemistry / Q000379:methods; D011812:Quinuclidines / Q000097:blood* / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012680:Sensitivity and Specificity; D000069464:Solifenacin Succinate; D044005:Tetrahydroisoquinolines / Q000097:blood* / Q000378:metabolism
D011812:Quinuclidines; D044005:Tetrahydroisoquinolines; D000069464:Solifenacin Succinate