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A Rapid and Sensitive Method for the Pharmacokinetic Study of Janumet (Sitagliptin and Metformin) Tablets by LC-MS/MS Coupled with Ion-Pair Solid Phase Extraction

Author(s):

Xiaonian Han*, Jing Wang, Jing Huang and Lirong Peng   Pages 1 - 9 ( 9 )

Abstract:


Background: As first-line treatments for diabetes, sitagliptin and metformin have been widely prescribed as combination to enhance the therapeutic effect. Objective: To establish a methodology to simultaneously monitor the two drugs in vivo by a reversed-phase liquid chromatography - tandem mass spectrometric (LC-MS/MS) method. Method: The two drugs were extracted from 50 µl human plasma by ion-pair solid phase extraction. The separation of the plasma samples was implemented on an Agilent Zorbax SB-CN column (150×4.6 mm, 5.0 µm). The mobile phase was the mixture (80:20, v/v) of methanol and 5.0 mM ammonium formate in water (pH 4.5). An ion trap spectrometer equipped with an electrospray ionization source was utilized to detect the elution in positive mode. Quantification of the analytes was achieved by multiple reaction monitoring (MRM) using the transitions of m/z 408.3→235.1 for sitagliptin and m/z 130.1→ 60.2 for metformin. Results: Sitagliptin and metformin demonstrated good linearity among the range of 1.00-1000 ng/mL and 5.00-4000 ng/mL. The intra-day and inter-day investigations displayed precisions of ≤ 3.6% and an accuracy range of -7.5% to 6.0% for the two drugs. The mean recovery of the two drugs was 96.0% and 98.5%. Under mandatory storage conditions, both the drugs gave an acceptable stability. The throughput of the assay was found to be more than 100 plasma samples per day ascribed to the run time of 3.0 min for each sample. Conclusion: The developed method was successfully applied to a pharmacokinetic study for a fixed-dose tablet formulation containing 50 mg sitagliptin and 500 mg metformin in 12 healthy volunteers.

Keywords:

Type 2 diabetes mellitus, pharmacokinetics, liquid chromatography, tandem mass spectrometry, sitagliptin, metformin

Affiliation:

Xi`an central hospital, Pharmacy Department, No.185, Houzaimen, North Street, Northwest University, College of Life Science, Xi`an central hospital, Pharmacy Department, Xi`an central hospital, Pharmacy Department



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