Simple And Rapid Analysis Of Linagliptin In Dried Blood Spot Using An Ionic Liquid Based Vortex-Assisted Dispersive Liquid-Liquid Microextraction Coupled With Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry: Application To Pharmacokinetic Studies

A simple, rapid, and convenient ionic liquid based vortex-assisted dispersive liquid-liquid micro extraction method for the determination of Linagliptin was developed. The main novelty of the present work deals with the analysis of Linagliptin in dried blood spot with significant advantages with regard to invasive sampling, volume of blood used (< 20 mu L), storage and transport of biological materials and requirements for special biohazard arrangements. The extraction sample was assayed using liquid chromatography-tandem mass spectrometry using electropray ionization techniques. The effects of significant factors in extracting and disperser solvent, and salt contents were investigated. An efficient quantification method was developed for bioassay of Linagliptin using Sitagliptin as internal standard through Inertsil ODS-3V (250 mm x 4.6 mm, 5 mu m) column using 10 mM ammonium acetate buffer (pH adjusted to 4.6 with 0.1% Trifluoroacetic acid): Acetonitrile [10:90 (v/v)] as mobile phase. Tandem mass spectrometry detection was performed to monitor precursor -> product ion transitions m/z 473.3 -> 364.2 for Linagliptin, m/z 408.2 -> 235.1 for internal standard. The assay was linear from 6 to 1500 ng/mL and the mean recoveries are more than 90%. The peak dried blood spot concentration (C-max) after 1.5 h was determined to be 1391.2 ng/ml for Linagliptin.