HPLC-UV METHOD FOR QUANTIFICATION OF SCHIZANDROL A IN RAT PLASMA: VALIDATION AND APPLICATION TO A PHARMACOKINETIC STUDY

Abstract

Schisandrol A is the most abundant and active component (dibenzocyclooctadiene lignan) isolated from seeds of Schizandra shinensis. it possesses hepatoprotective, antiviral, antioxidant, cytotoxic, and cancer chemopreventive activities (1). The purpose of the present work was to develop and validate a simple and reliable method for the determination of schizan drol A in rat plasma and to use it for the estimation of the pharmacokinetic parameters of schizandrol A. A simple, specific and sensitive RP-h Pl C method with UV detection for the determination of schizandrol A in plasma was developed and validated. from a variety of compounds and solvents tested, abietic acid was selected as the internal standard and acetonitril was found to be the best solvent for extracting schizan drol A from plasma. hPl C analysis of the extracts was performed on a C 18 column (4.6 mm ×150 mm, 5 µm particle size) equipped witch a guard pre-column (same sorbent 2.0 mm). The mobile phase for gradi ent elution consisted of two solvent systems: solvent A 0.03 % (v/v) water solution of trifluoroacetic acid; solvent b methanol. The UV detection was at 250 nm. The elution time for schizandrol A and abietic acid was approximately 7.3 and 25.9 min, respectively. The calibration curve of schizandrol A was linear (r>0.99) over the range 0.10–10 µg/ml in rat plasma. Recovery from plasma was 84–98 %. The limit of detection (l Od) and limit of quantification ( l Oq) for schizandrol A were 0.03 and 0.10 µg/m, respectively. The validated method was successfully applied to the pharmacoki netic study of schizandrol A in rat plasma after single oral administration of Schizandra oil extract (dose of schizandrol A 5 mg/kg). The basic pharmacokinetic parameters of schizandrol A in rats were determined by noncompartmental analysis. The mean AUC 0-t and C max were 3.26 h∙µg/ml and 0.56 µg/ml The peak plas ma levels was achieved to 1.0 hour and the mean elimi nation half life was 3.06 hours. Reference: 1. Min h. y. et al. (2008) bioorg. Med. Chem. lett. 18: 523–526.