Cimetidine Quantification in Human Plasma by High-performance
Liquid Chromatography Coupled to Electrospray
Ionization Tandem Mass Spectrometry. Application
to a Comparative Pharmacokinetics Study |
Moreno RA1,2, Oliveira CostaI3, Brum Junior L4, Sverdloff CE1,2, Domingues CC1,
Borges DC5, Oliveira RA1, Borges NC1,6* |
1Synchrophar Assessoria e Desenvolvimento de Projetos Clínicos, Campinas, SP, Brazil |
| 2Department of Pharmacology, Faculty of Medical Sciences, State University of Campinas (UNICAMP), Campinas, SP, Brazil |
| 3Department of Bioequivalence, Hermes Pardini Institute, Belo Horizonte, MG, Brazil |
| 4Multilab Indústria e Comércio de Produtos Farmacêuticos Ltda, Sao Jerônimo, RS, Brazil |
| 5Jundiai Faculty of Medicine, Jundiai, SP, Brazil |
| 6Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, SP, Brazil |
| *Corresponding author: |
Dr. Ney Carter C. Borges,
24 Cesar Bierrenbach
Street,
Campinas, SP, Brazil,
Postal
Code: 13015-025,
Tel/Fax: 55 19
3234-2834,
E-mail : medney@synchrophar.com |
|
| Received September 11, 2009; Accepted December 14, 2009; Published
December 15, 2009 |
Citation: Moreno RA, CostaI O, Brum Junior L, Sverdloff CE, Domingues
CC, et al. (2009) Cimetidine Quantification in Human Plasma by Highperformance
Liquid Chromatography Coupled to Electrospray Ionization
Tandem Mass Spectrometry. Application to a Comparative Pharmacokinetics
Study. J Bioanal Biomed 1: 005-013. doi: 10.4172/1948-593X.1000002 |
Copyright: ©2009 Moreno RA, et al. This is an open-access article distributed under the terms of the Creative Commons
Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author
and source are credited. |
| Abstract |
A specific, fast and sensitive LC–MS/MS assay was developed
for the determination of cimetidine in human
plasma using nizatidine as the internal standard (IS). The
limit of quantification was 5.0 ng/ml and the method was
linear in the range of 5.0 to 5000 ng/ml. The cimetidine
and IS retention times were 1.35±0.3 and 1.40±0.03 min,
respectively. Method intra-batch precision and accuracy
ranged from 2.0 to 5.4%, and 92.1 to 103.7%, respectively.
Inter-batch precision ranged from 4.2 to 6.3%, while Inter-
batch accuracy ranged from 97.0 to 106.6%.
The analytical method was applied to evaluate the pharmacokinetic
and relative bioavailability of two different
pharmaceutical formulations containing 400 mg of
cimetidine containing. This study evaluated 29 volunteers
in a randomized, 2-period crossover study with 14 days
washout period between doses. The geometric mean and
respective 90% CI of cimetidine test/reference percent
ratios were 95.73% (87.76 - 104.43%) for Cmax, 100.80%
(95.98 - 105.96%) for AUC0-t and 100.90 (96.06 - 105.88)
for AUC0-inf. Based on the 90% confidence interval of the
individual ratios (test formulation/reference formulation)
for Cmax and AUC0-inf, it was concluded that the test formulation
is bioequivalent to the reference one with respect to
the rate and extent of absorption of cimetidine. In addition,
using the Kruskal-Wallis Test no statistical differences
of Tmax and the Cmax were observed related to the
sex of the volunteer. |
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