An HPLC/UV method for the determination of RGH-1756 in dog and rat plasma.
RGH-1756 (1-(2-methoxy-phenyl)-4-(4-[4-(6-imidazo[2,1-b]-thiazolyl)-phenoxy]-butyl)-piperazine dimethansulphonate) is a novel atypical antipsychotic candidate of Gedeon Richter Ltd. A new HPLC method has been developed and validated for the quantitative determination of RGH-1756 in dog and rat plasma. The compound and the internal standard are extracted from the biological samples by a simple and fast liquid--liquid extraction method, using 1-chlorobutane. The recovery for RGH-1756 is about 90%. The extracts are analyzed by reversed phase HPLC (column: Supelcosil-LC-18-DB 250*4.6 mm, 5 microm, eluent:acetonitrile:methanol:0.2 molar ammonium-acetate 40:25:35, lambda=254 nm). The assay is specific for RGH-1756. The standard curves are linear in the range between 10 and 2000 ng ml(-1). The overall precision (expressed as CV%) and accuracy (expressed as bias%) of quality controls and calibration standards are within 15%. The validated lower limit of quantification is 10 ng/ml. No indications have been found for possible instabilities of RGH-1756 in plasma, in the extraction solvent, or after repeated thawing-freezing cycles. The method has been succesfully applied for the bioavailability studies of RGH-1756 in the two animal species. In these studies results of the inprocess method validation have shown the reliability of the method, too. CV% of quality controls in the rat study has been found between 7.4 and 10.0%, in the dog study between 4.1 and 12.5%. The bias has ranged from 0.4 to 3.8% and from -4.5 to 1.2% in the rat and dog study, respectively.
Terjéki
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Laboratory of Pharmacokinetics, Gedeon Richter Ltd., 1103 Budapest, Gyömröi út 19-21, Budapest, Hungary. e.terjeki@richter.hu
Kapás
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D000818:Animals; D014150:Antipsychotic Agents / Q000097:blood* / Q000493:pharmacokinetics; D001682:Biological Availability; D002138:Calibration; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004285:Dogs; D005260:Female; D008297:Male; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013056:Spectrophotometry, Ultraviolet / Q000379:methods*; D013844:Thiazoles / Q000097:blood* / Q000493:pharmacokinetics
C427703:1-(2-methoxy-phenyl)-4-(4-(4-(6-imidazol(2,1-b) thiazolyl)-phenoxy)-butyl-4-(14)C)-piperazine dimethane; D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles