生物学的同等性とバイオアベイラビリティのジャーナル

概要

Determination of Amtolmetin and Its Active Metabolites in Plasma by HPLC-UV: Application to a Bioequivalence Study

Punnamchand Loya and Madhusudan N. Saraf

A simple, rapid and selective method was developed for the determination of amtolmetin guacil, tolmetin so dium and tolmetin glycinamide from human plasma. The method in- volves extracting amtolmetin guacil, tolmetin sodiu m and tolmetin glycinamide with acetonitrile using coumar in as internal standard. Chromatographic separation was c arried out on a C8 column using mixture of acetonitrile:me thanol: 1% acetic acid as mobile phase with UV detection se t at 313 nm. The retention time of AG, T, TG and IS were 8.20 ± 0.2, 5.3 ± 0.2, 4.0 ± 0.2 and 4.9 ± 0.2 min, respectively. The method was validated and found to be linear in the range of 0.5-20.0 μ g/ml for amtolmetin guacil, tolmetin sodium and tolmetin glycinamide. The co-efficient o f varia- tion for intra-day and inter-day accuracy and preci sion was <8.2 % for amtolmetin guacil, tolmetin sodium and t olmetin glycinamide. An open, randomized, two-treatment, tw o pe- riod, single dose crossover, bioequivalence study i n twelve fasting, healthy, male, volunteers was conducted. A fter dos- ing, serial blood samples were collected for the pe riod of 24 h. Various pharmacokinetic parameters for both the active metabolites (tolmetin and tolmetin glycinamide) wer e de- termined from plasma concentration of both formulat ions. Log transformed values were compared by analysis of vari- ance (ANOVA) followed by classical 90% confidence i n- terval for C max , AUC 0-t and AUC 0-inf for both the active me- tabolites (tolmetin and tolmetin glycinamide) and i t was found that both test and reference products were bioequivalent. The proposed method proved to be rapid, precise and accurate and can be successfully used i n a bioequivalence study of amtolmetin guacil tablet.