LC fluorescence method for multiple synthetic compounds to rapidly create in vivo pharmacokinetic database utilizing 'N-in-One' dosing

J Pharm Biomed Anal. 2001 Nov;26(4):519-30. doi: 10.1016/s0731-7085(01)00452-6.

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.

MeSH terms

  • Animals
  • Chromatography, High Pressure Liquid
  • Half-Life
  • Injections, Intravenous
  • Male
  • Metabolic Clearance Rate
  • Piperazines / blood
  • Piperazines / chemical synthesis
  • Piperazines / pharmacokinetics*
  • Quality Control
  • Rats
  • Rats, Sprague-Dawley
  • Regression Analysis
  • Structure-Activity Relationship

Substances

  • Piperazines