Determination of Liraglutide in Rat Plasma by a Selective Liquid Chromatography-tandem Mass Spectrometry Method: Application to a Pharmacokinetics Study

A simple, sensitive and selective LC-MS/MS method was developed for the quantitative analysis of liraglutide and validated in rat plasma. Human insulin was used as the internal standard. After a simple protein precipitation step, liraglutide was chromatographically separated using an InertSustain Bio C18 column with mobile phases comprising acetonitrile with 0.1% formic acid (A) and water with 0.1% formic acid (B). Detection was achieved using positive ion electrospray ionization in multiple-reaction monitoring (MRM) mode. Good linearity was observed in the concentration range 0.5-250 ng/mL (r > 0.99). The intra- and inter-day precision values (expressed as relative standard deviation, RSD) of liraglutide ranged from 1.97-7.63% and 5.25-11.9, respectively. The accuracy (expressed as relative error, RE) ranged from -8.79-11.4%. Both the recovery and matrix effect were within acceptable limits. This method was successfully applied for the pharmacokinetics study of liraglutide in rats after subcutaneous administration.