Development of a UHPLC-MS/MS method for the quantification of Pristinamycin IA and IIA in beagle dog plasma and its pharmacokinetic application

The aim of this study was to develop and fully validate a sensitive and rapid ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method for simultaneous quantification of pristinamycin IA (PIA) and pristinamycin IIA (PIIA) in plasma of beagle dogs after oral administration of pristinamycin tablets. PIA, PIIA and quinupristin (internal standard, IS) were separated on an Agilent Eclipse Plus C 18 column (2.1 mm x 100 mm, 3.5 mu m particle size) by using gradient elution consisting of methanol and water (0.1 % formic acid) at a flow rate of 0.4 mL/min in 4.0 min. Multiple reaction monitoring (MRM) mode was performed to quantify data under monitoring precursor-product ion transitions of m/z 867.6-*134.1, 548.4-*287.1 and 1022.7-*133.9 for PIA, PIIA and IS at positive ion mode, respectively. The method was developed at linearity ranging from 1.0 to 1000 ng/mL for all analytes.The accuracy of PIA and PIIA was observed to range between-10.6 % and 7.1 %, while the precision was found to be within 8.9 %. No significant matrix effect was observed. PIA and PIIA demonstrated stability during sample storage, preparation and analytic procedures. Furthermore, this method was successfully applied in the investigation of the pharmacokinetic profile of PIA and PIIA in beagle dogs after oral administration of pristinamycin tablets (75 mg for PIA and 175 mg for PIIA). The biological half-life (t1/2) 1/2 ) was determined to be 1.75 f 0.07 hand 1.44 f 0.31 h for PIA and PIIA, respectively. The areas under curves (AUC0-t) 0-t ) of PIA and PIIA were 80.7 f 24.6 and 230 f 94.8 mu g/L center dot h, respectively.