Determination of Amtolmetin and Its Active Metabolites in Plasma by HPLC-UV: Application to a Bioequivalence Study
Title:
Determination of Amtolmetin and Its Active Metabolites in Plasma by HPLC-UV: Application to a Bioequivalence Study
Author:
Punnamchand Loya Madhusudan N. Saraf
Appeared in:
Journal of bioequivalence & bioavailability
Paging:
Volume 02 (2010) nr. 02 pages 037-044
Year:
2010
Contents:
A simple, rapid and selective method was developed forthe determination of amtolmetin guacil, tolmetin sodium andtolmetin glycinamide from human plasma. The method involvesextracting amtolmetin guacil, tolmetin sodium andtolmetin glycinamide with acetonitrile using coumarin asinternal standard. Chromatographic separation was carriedout on a C8 column using mixture of acetonitrile:methanol:1% acetic acid as mobile phase with UV detection set at313 nm. The retention time of AG, T, TG and IS were8.20±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 therange of 0.5-20.0 μg/ml for amtolmetin guacil, tolmetinsodium and tolmetin glycinamide. The co-efficient of variationfor intra-day and inter-day accuracy and precision was<8.2 % for amtolmetin guacil, tolmetin sodium and tolmetinglycinamide. An open, randomized, two-treatment, two period,single dose crossover, bioequivalence study in twelvefasting, healthy, male, volunteers was conducted. After dosing,serial blood samples were collected for the period of 24h. Various pharmacokinetic parameters for both the activemetabolites (tolmetin and tolmetin glycinamide) were determinedfrom plasma concentration of both formulations.Log transformed values were compared by analysis of variance(ANOVA) followed by classical 90% confidence intervalfor Cmax, AUC0-t and AUC0-inf for both the active metabolites(tolmetin and tolmetin glycinamide) and it wasfound that both test and reference products werebioequivalent. The proposed method proved to be rapid,precise and accurate and can be successfully used in abioequivalence study of amtolmetin guacil tablet.
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