Titre du document / Document title

Simultaneous determination of metformin and gliclazide in human plasma by liquid chromatography-tandem mass spectrometry : application to a bioequivalence study of two formulations in healthy volunteers

Auteur(s) / Author(s)

ZHONG Guo-Ping ⁽¹⁾ ; BI Hui-Chang ⁽¹⁾ ; SHUFENG ZHOU ⁽²⁾ ; XIAO CHEN ⁽³⁾ ; MIN HUANG ⁽¹⁾ ;

Affiliation(s) du ou des auteurs / Author(s) Affiliation(s)

⁽¹⁾ Institute of Clinical Pharmacology, School of Pharmaceutical Sciences, Sun Yat-sen University, 74 Zhongshan Road II, Guangzhou 510080, CHINE
⁽²⁾ Department of Pharmacy, Faculty of Science, National University of Singapore, SINGAPOUR
⁽³⁾ Department of Pharmacy, the First Affiliated Hospital, Sun Yat-sen University, 58 Zhongshan Road, Guangzhou 510080, CHINE

Résumé / Abstract

A rapid and sensitive liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed and validated to simultaneously determine gliclazide and metformin in human plasma using huperzine A as the internal standard (IS). After acetonitrile-induced protein precipitation of the plasma samples, gliclazide, metformin and the IS were subjected to LC/MS/MS analysis using electro-spray ionization (ESI). Chromatographic separation was performed on a Hypersil BDS C₁₈ column (50 mm x 2.1 mm, i.d., 3 μm). The method had a chromatographic running time of 2.0 min and linear calibration curves over the concentration ranges of10-10 000 ng ml^-1 for gliclazide and 7.8-4678.9 ng ml^-1 for metformin. The recoveries of the method were found to be 71-104%. The lower limits of quantification (LOQ) of the method were 10.0 and 7.8 ng ml^-1 for gliclazide and metformin, respectively. The intra-and interday precision was less than 15% for all quality control samples at concentrations of 100, 500, and 2000 ng ml^-1. The validated LC/MS/MS method has been used to study bioequivalence in healthy volunteers. These results indicate that the method was efficient with a very short running time (2.0 min) for metformin and gliclazide compared to the methods reported in the literature. The presented method had acceptable accuracy, precision and sensitivity and was used in clinical bioequivalence study.

Revue / Journal Title

Journal of mass spectrometry   ISSN 1076-5174 

Source / Source

2005, vol. 40, n^o11, pp. 1462-1471 [10 page(s) (article)] (36 ref.)

Langue / Language

Anglais

Editeur / Publisher

Wiley, Chichester, ROYAUME-UNI  (1995) (Revue)

Mots-clés anglais / English Keywords

Sulfonylureas ; Biguanides ; HPLC chromatography ; Mass spectrometry MS/MS ; Coupled method ; Blood ; Biological fluid ; Hypoglycemic agent ; Quantitative analysis ; Oral administration ; Validation ; Reversed phase chromatography ; Bioavailability ; Pharmacokinetics ; Volunteer ; Normal ; Formulation ; Bioequivalence ; Blood plasma ; Human ; Gliclazide ; Metformin ; Chemical analysis ; Simultaneous measurement ;

Mots-clés français / French Keywords

Sulfonylurées ; Biguanides ; LC MS MS ; Chromatographie HPLC ; Spectrométrie masse tandem ; Méthode couplée ; Sang ; Liquide biologique ; Hypoglycémiant ; Analyse quantitative ; Voie orale ; Validation ; Chromatographie phase inverse ; Biodisponibilité ; Pharmacocinétique ; Volontaire ; Normal ; Formulation ; Bioéquivalence ; Plasma sanguin ; Homme ; Gliclazide ; Metformine ; Analyse chimique ; Mesure simultanée ;

Mots-clés espagnols / Spanish Keywords

Sulfonilureas ; Biguanidas ; Cromatografía HPLC ; Espectrometría masa en tándem ; Método acoplado ; Sangre ; Líquido biológico ; Hipoglicemiante ; Análisis cuantitativo ; Vía oral ; Validación ; Cromatografía fase inversa ; Biodisponibilidad ; Farmacocinética ; Voluntario ; Normal ; Formulación ; Bioequivalencia ; Plasma sanguíneo ; Hombre ; Gliclazida ; Metformina ; Análisis químico ; Medición simultánea ;

Mots-clés d'auteur / Author Keywords

metformin ; gliclazide ; liquid chromatography/tandem mass spectrometry ; pharmacokinetics ; bioavailability ; bioequivalence ;

Localisation / Location

INIST-CNRS, Cote INIST : 22950, 35400013551925.0070