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.

Simultaneous determination of YM928, a novel noncompetitive AMPA receptor antagonist, and its demethylated metabolite in rat, dog and monkey plasma by high-performance liquid chromatography with ultraviolet detection.

A specific HPLC method for the simultaneous determination of YM928, a novel noncompetitive AMPA receptor antagonist, and its demethylated metabolite (YM-58875) in rat, dog and monkey plasma was developed and validated. The method utilized multiple-step liquid-liquid extraction followed by a reversed-phase HPLC with UV detection at 275 nm. No interfering peaks were observed at the retention times of YM928, YM-58875 or internal standard. The validated quantitation range was 5-5000 ng/mL for both YM928 and YM-58875 when 1 mL of the plasma sample was used. The intra- and inter-day precision was less than 5.3 and 2.5% for YM928, and 3.7 and 2.3% for YM-58875, respectively. The intra- and inter-day accuracies were -8.7-5.3% and 0.7-1.9% for YM928, and -10.0-6.1% and 1.3-3.4% for YM-58875, respectively. The mean recoveries in the extraction process were 52.7-62.8%. The utility of this analytical method was demonstrated by the investigation of the pharmacokinetics of the unchanged drug and its metabolite in preclinical studies.

LC determination of YM466, a new factor Xa inhibitor, in rat and dog plasma.

A specific method for the determination of YM466, a novel Factor Xa inhibitor, in rat and dog plasma was developed and validated. YM466 was extracted from plasma by solid-phase extraction and analyzed by UV-HPLC at an absorbance wavelength of 240 nm. The intra-day precision and accuracy ranged from 0.8 to 2.4% and 0.1 to 5.0% in rats, and from 1.6 to 2.4% and 0.0 to 4.1% in dogs, respectively. The lower limit of quantification was 10 ng/ml when 1 ml of plasma was used. No endogenous interference was observed in the plasma of rats and dogs.