title: Simultaneous determination of sitagliptin and simvastatin in human plasma by LC-MS/MS and its application to a human pharmacokinetic study.
abstract: A simple, rapid and sensitive liquid chromatography-tandem mass spectrometric (LC-MS/MS) assay method has been developed and validated for simultaneous quantification of sitagliptin and simvastatin in human plasma. Carbamazepine was used as an internal standard (IS). The analytes and IS were extracted from the human plasma by liquid-liquid extraction technique. The reconstituted samples were chromatographed on an Alltima HP C(18) column using an isocratic solvent mixture [acetonitrile-5 mm ammonium acetate (pH 4.5), 85:15 (v/v)] at a flow rate of 1.0 mL/min. Method validation was performed as per Food and Drug Administration guidelines and the results met the acceptance criteria. The calibration curves obtained were linear (r(2)  ≥ 0.99) over the concentration range of 0.10-501 and 0.05-105 ng/mL for sitagliptin and simvastatin, respectively. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. Both the analytes were found to be stable in a battery of stability studies. The method is precise and sensitive enough for its intended purpose. A run time of 3.0 min for each sample made it possible to analyze more than 300 plasma samples per day. The developed assay was successfully applied to a pharmacokinetic study in human volunteers.
authors.affiliation: University College of Pharmaceutical Sciences, Jawaharlal Nehru Technological University, Kukatpally, Hyderabad, India.
authors.forename: Laxminarayana
authors.initials: L
authors.lastname: Burugula
authors.forename: Ramesh
authors.initials: R
authors.lastname: Mullangi
authors.forename: Nageswara Rao
authors.initials: NR
authors.lastname: Pilli
authors.forename: Ajitha
authors.initials: A
authors.lastname: Makula
authors.forename: Durga Srinivas
authors.initials: DS
authors.lastname: Lodagala
authors.forename: Rajnarayana
authors.initials: R
authors.lastname: Kandhagatla
mesh_terms: D000284:Administration, Oral; D002853:Chromatography, Liquid / Q000379:methods*; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D004355:Drug Stability; D006801:Humans; D016018:Least-Squares Analysis; D059625:Liquid-Liquid Extraction / Q000379:methods; D008297:Male; D011719:Pyrazines / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019821:Simvastatin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D000068900:Sitagliptin Phosphate; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000008:administration & dosage / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors; D011719:Pyrazines; D014230:Triazoles; D019821:Simvastatin; D000068900:Sitagliptin Phosphate