Determination Of Arbidol In Human Plasma By High Performance Liquid Chromatography And Study On Bioequivalence

ObjectivesA highly sensitive and selective high performance liquid chromatographic method (HPLC) was developed and validated for the determination of arbidol in healthy human plasma.To evaluate the bioavailability of arbidol hydrochloride tablets and capsules following oral administration to healthy male volunteers by 90% confidence interval.Methods18 healthy Chinese male volunteers were enrolled following a single dose oral administration of arbidol hydrochloride in test or reference 200 mg respectively by randomized tri-crossover design.The method involves the liquid-liquid extraction of drug and internal standard (IS) from plasma followed by evaporation and reconstitution in mobile phase. The assay was conducted on the Hypersil C4 (150 mm(?)4．6 mm, 5 (?)m) columnn with methanol-0．05 mol(?)L ammonium dihydrogen phosphate-triethylamine (60: 40: 0．4, pH 3．5) as the mobile phase. The detection wavelength was set at 315 nm, and the indometacin was taken as the internal standard.Plasma concentrations of arbidol were analyzed by HPLC, and the main pharmacokinetic parameters of arbidol hydrochloride tablets in test, capsules in test and capsules in reference were caculated by 3p97, and the bioequivanlence were estimated by 90% confidence interval ( 90% CI).Results The limit of quantification (LOQ) for arbidol in plasma was 0．005 (?)g(?)mL. The linearity range was 0．01 (?) 2 (?)g(?)mL with a regressive equation of Height Ratio= 2．l69AmtRatio+0．029, r=0．997．The recovery were proven above 85% and the intra-day RSD and inter-day RSD below 15%.The main pharmacokinetic parameters of arbidol hydrochloride tablets in test, capsules in test and capsules in reference were shown as following: C were 1．153(?) 0．111 (?)g(?)mL, 1．088(?)0．142 (?)g(?)mL and 1．067(?)0．133 (?)g(?)mL; T were 0．707 (?)0．107 h, 0．707(?)0．107 h and 0．688(?)0．078 h; AUC were 5．783(?)1．108 (?)g(?)h(?)mL, 5．227(?)0．816 (?)g(?)h(?)mL and 5．275(?)0．736 (?)g(?)h(?)mL; AUC were 6．894(?)1．053 (?)g(?)h(?)mL, 6．964(?)0．872 (?)g(?)h(?)mL and 6．865(?)0．805 (?)g(?)h(?)mL. Caculated with AUC, the bioavailability of the tablets in test and capsules in test were 109．1(?)10．7% and 99．0(?)7．3%.Compared with the capsules in reference, the 90% confidence interval of the main pharmacokinetic parameters of arbidol hydrochloride tablets in test and capsules in test were as following: 90% CI of C were 104．4%(?)112．9% and 97．6%(?)106．8%; 90% CI of AUC were 104．1%(?)113．3% and 96．0%(?)101．7%; 90% CI of AUC were 95．8%(?)104．4% and 97．6%(?)106．8%.ConculsionsThe method was proven to be convenient, rapid, accurate, and suitable for the pharmocokinetics study of arbidol and monitoring its concentration for the clinical application.According to the acceptance range, 90% CI of AUC within 80% (?)125% and 90% CI of C within 70%(?)143%, the results of statistical analysis showed that there was no significant difference among the parameters of arbidol hydrochloride tablets in test, capsules in test, and capsules in reference. They were proven to be bioequivalant.