title: LC fluorescence method for multiple synthetic compounds to rapidly create in vivo pharmacokinetic database utilizing 'N-in-One' dosing.
abstract: This manuscript reports development and validation of an assay method in rat serum for the simultaneous estimation of C1, C2, and C3, in-house CDRI molecules, of the class of aryloxy-substituted aryl-piperazinyl derivatives. The assay was applied to determine pharmacokinetic data after simultaneous intravenous administration of these three compounds. A high-performance liquid chromatography assay method using isocratic elution and fluorescence (excitation, 250 nm; emission 350 nm) was developed for simultaneous estimation of all the three compounds in rat serum. Linearity was observed between 12.5 and 400 ng/ml for all the three compounds in serum. Recoveries were highly consistent over the concentration ranges for all the analytes. Variations in the intra- and inter-batch accuracy and precision were within the acceptable limits of +/-20% at the limit of quantitation, whereas at higher concentrations it was +/-15%. A mixture of the three compounds was administered intravenously to rats. Blood samples were collected over a period of 6 h and analyzed to determine serum levels and pharmacokinetics of each compound. The pharmacokinetics of the aforementioned three compounds was also determined after individual administration. The results obtained in the N-in-One dosing correlated well with discrete dosing of compounds. Based on the results obtained, C2 emerges to be the compound with appropriate pharmacokinetic parameters. Thus, the N-in-One method is a useful method for increasing the throughput to obtain the pharmacokinetic information.
authors.affiliation: Department of Pharmacokinetics and Metabolism, Central Drug Research Institute, Post Box 173, Lucknow 226001, India.
authors.forename: M
authors.initials: M
authors.lastname: Rajanikanth
authors.forename: R C
authors.initials: RC
authors.lastname: Gupta
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D007275:Injections, Intravenous; D008297:Male; D008657:Metabolic Clearance Rate; D010879:Piperazines / Q000097:blood / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D011786:Quality Control; D051381:Rats; D017207:Rats, Sprague-Dawley; D012044:Regression Analysis; D013329:Structure-Activity Relationship
chemical_list: D010879:Piperazines