Quantitative determination and pharmacokinetics of a new antipsychotic (CGS 13429A) in human plasma using capillary gas chromatography/mass spectrometry

3区 · 医学

Article

作者: S. Carlsen ; M.L. Powell ; M. Hayes

A quantitative analytical method is described for the determination of a new antipsychotic (CGS 13429A) in human plasma. The method relies on capillary gas chromatography/mass spectrometry in the positive chemical ionization mode, utilizing ammonia reagent gas. The limit of quantification (LOQ) was 0.1 ng ml-1 and the method was validated over a concentration range of 0.1-50 ng ml-1. The method was used to measure CGS 13429A plasma concentrations following the administration of single oral ascending doses ranging from 0.1 to 10 mg in healthy male volunteers. The drug was rapidly absorbed (Tmax ranged from 1.1 to 3.7 h) and showed a mean terminal elimination half-life of 8.1 h, which was independent of dose. Area-under-the-curve (AUC) along with Cmax values were proportional to the administered dose.

1991-09-01·Drug Metabolism and Disposition

Determination of in vivo hepatic extraction ratio from in vitro metabolism by rat hepatocytes.

作者: Douglas, Frank L. ; Tripp, Spencer L. ; Dunton, Alan W. ; Rakhit, Ashok ; Singh, Kuldeep

Using isolated rat hepatocytes, the in vitro intrinsic hepatic clearance of three drugs, namely, antipyrine (AP), propranolol (P), and CGS 13429 was determinedThe hepatic extraction ratios of AP, P, and CGS 13429 were then calculated to be 0.10, 0.90, and 0.88, resp.To determine the in vivo hepatic extraction ratio in the rat, AP, P, or CGs 13429 was infused sep. at a rate of 40, 20, and 20 μg/min.kg, via jugular and hepatic portal veins.The steady state plasma levels of AP, P, and CGS 13429 were 5.30 μg/mL, 608 and 380 ng/mL after jugular vein (i.v.) infusions, and 4.96 μg/mL, 162, and 146 ng/mL after hepatic portal vein (hpv) infusions, resp.The blood to plasma ratios of AP, P, and CGS 13429 were 1.0, 0.78, and 1.0, resp.The in vivo hepatic extraction ratio, calculated as (C_ss_,_iv - C_ss_,_hpv)/C_ss_,_iv from steady state blood levels following i.v. and hpv infusions for AP, P, and CGS 13429, were 0.065, 0.73, and 0.61, resp.These results suggest that in vitro metabolism studies by hepatocytes may have potential application, during drug discovery, to distinguish drugs of low and high metabolic hepatic extraction ratio in vivo.

1989-01-01·Journal of Chromatography B: Biomedical Sciences and Applications

High-performance liquid chromatographic method for a clozapine analogue, CGS 13429, and its N-oxide and desmethyl metabolites

Article

作者: Jeannette D. Vermeulen ; James P. Chovan

An HPLC method for preclin. pharmacokinetic and bioavailability studies to quantify a clozapine analog, CGS 13429 (I), and its N-dimethyl and N-oxide metabolite is described.The limit of detection was 40 ng/mL for 200 μL of rat or dog plasma for all 3 compoundsThe clozapine analog CGS 11760 was used as internal standard

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