Simple, Rapid and Validated LC Determination of Lopinavir in Rat Plasma and Its Application in Pharmacokinetic Studies

Rahul Vats

doi:10.3797/scipharm.1107-24

Abstract

Lopinavir is a new specific and potent HIV-1 protease inhibitor. A simple and rapid Reverse Phase High-Performance Liquid Chromatographic method using UV detection was developed and validated for the analysis of lopinavir in rat plasma under isocratic conditions. The method involves a single step protein precipitation technique. The detector response was linear over the concentration range of 250 to 4000 ng mL −1. High recovery ranging from 97.5 to 101.2 percent was obtained which precludes the use of internal standard. The developed method was validated as per standard guidelines. Validation of the developed method demonstrated accuracy, precision and selectivity of the proposed method. The drug was found to be stable under various processing and storage conditions. This rapid and cost-effective method was successfully applied in the estimation of lopinavir and determination of various pharmacokinetic parameters during post intravenous bolus administration of the drug in rats. The developed method can be suitably employed in preclinical pharmacokinetic evaluation of new formulations designed to improve the bioavailability of lopinavir.

Highlights

Lopinavir (LPV) is a potent HIV protease inhibitor (PI) and a key ingredient of Highly Active Anti-Retroviral Therapy (HAART) [1]
RTV is coadministered with LPV orally in HAART in order to improve the bioavailability of LPV
Such delivery systems will avoid heavy pill burden of LPV and RTV co-formulation, and improve patient compliance and adherence to therapy which are very vital for treatment against HIV/AIDS

Summary

Introduction

Lopinavir (LPV) is a potent HIV protease inhibitor (PI) and a key ingredient of Highly Active Anti-Retroviral Therapy (HAART) [1]. LPV was developed by Abbott Laboratories to improve pharmacokinetics and to reduce HIV resistance of the company's earlier protease inhibitor, Ritonavir (RTV) [2]. Several research groups have been working on the development of novel delivery systems containing LPV alone in the effective treatment of HIV/AIDS. Such delivery systems will avoid heavy pill burden of LPV and RTV co-formulation, and improve patient compliance and adherence to therapy which are very vital for treatment against HIV/AIDS. Researchers have tried to improve solubility and bioavailability of LPV using microparticulate and nanocarrier systems [7, 8]. Such research endeavors need a simple, rapid and costeffective bioanalytical method to quantify the LPV concentration in rat plasma

Methods

Results

Conclusion