title: Liquid chromatography-tandem mass spectrometry simultaneous determination of repaglinide and metformin in human plasma and its application to bioequivalence study.
abstract: A simple, sensitive, selective, and reproducible liquid chromatography-tandem mass spectrometric method was developed for the simultaneous determination of repaglinide and metformin in human plasma using d5-repaglinide and d6-metformin as internal standards (ISs). After a simple protein precipitation using acetonitrile as the precipitation solvent, both analytes and ISs were separated on a Venusil ASB C 18 (150 mm x 4.6 mm, 5 microm) via gradient elution using acetonitrile--10 mmol x L(-1) ammonium acetate as the mobile phase. A chromatographic total run time of 7.5 min was achieved. Mass spectrometric detection was conducted with atmospheric pressure chemical ionization under positive-ion and multiple-reaction monitoring modes. The method was linear over the 0.2 to 60.0 ng x mL(-1) concentration range for repaglinide and over the 4 to 1 000 ng x mL(-1) range for metformin. For both analytes, the intra- and inter-accuracies and precisions were within the +/- 15% acceptable limit across all concentrations. The validated method was successfully applied to a clinical bioequivalence study.
authors.affiliation: Zhejiang University of Technology, Hangzhou 310014, China.
authors.forename: Xiao-Rong
authors.initials: XR
authors.lastname: Liang
authors.forename: Xiao-Jian
authors.initials: XJ
authors.lastname: Dai
authors.forename: Yi-Fan
authors.initials: YF
authors.lastname: Zhang
authors.forename: Jue-Fang
authors.initials: JF
authors.lastname: Ding
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Chen
authors.forename: Da-Fang
authors.initials: DF
authors.lastname: Zhong
mesh_terms: D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D019540:Area Under Curve; D002219:Carbamates / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004355:Drug Stability; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D008297:Male; D008687:Metformin / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D008875:Middle Aged; D010880:Piperidines / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics*; D053719:Tandem Mass Spectrometry; D013810:Therapeutic Equivalency; D055815:Young Adult
chemical_list: D002219:Carbamates; D007004:Hypoglycemic Agents; D010880:Piperidines; C072379:repaglinide; D008687:Metformin