Zeitschrift für Bioanalyse und Biomedizin

Cimetidine Quantification in Human Plasma by High-performance Liquid Chromatography Coupled to Electrospray Ionization Tandem Mass Spectrometry. Application to a Comparative Pharmacokinetics Study

Abstract

Moreno RA, Oliveira CostaI, Brum Junior L, Sverdloff CE, Domingues CC, Borges DC, Oliveira RA and Borges NC

A specific, fast and sensitive LC–MS/MS assay was d e- veloped for the determination of cimetidine in huma n plasma using nizatidine as the internal standard (I S). The limit of quantification was 5.0 ng/ml and the metho d was linear in the range of 5.0 to 5000 ng/ml. The cimet idine and IS retention times were 1.35±0.3 and 1.40±0.03 min, respectively. Method intra-batch precision and accu racy ranged from 2.0 to 5.4%, and 92.1 to 103.7%, respec tively. Inter-batch precision ranged from 4.2 to 6.3%, whil e In- ter-batch accuracy ranged from 97.0 to 106.6%.

The analytical method was applied to evaluate the p har- macokinetic and relative bioavailability of two dif ferent pharmaceutical formulations containing 400 mg of cimetidine containing. This study evaluated 29 volu nteers in a randomized, 2-period crossover study with 14 d ays washout period between doses. The geometric mean an d respective 90% CI of cimetidine test/reference perc ent ratios were 95.73% (87.76 - 104.43%) for C max, 100.80% (95.98 - 105.96%) for AUC 0-t and 100.90 (96.06 - 105.88) for AUC 0-inf . Based on the 90% confidence interval of the individual ratios (test formulation/reference formu lation) for C max and AUC 0-inf , it was concluded that the test formu- lation is bioequivalent to the reference one with r espect to the rate and extent of absorption of cimetidine. In addi- tion, using the Kruskal-Wallis Test no statistical differ- ences of Tmax and the Cmax were observed related to the sex of the volunteer.