doiSerbia

Development of a new ultra-high performance liquid chromatography - tandem mass spectrometry method for determination of ambroxol hydrochloride in serum with pharmacokinetic application

Vujović Maja M. (University of Niš, Faculty of Medicine, Niš , Serbia + Institute of Forensic Medicine, Toxicology Laboratory, Niš, Serbia)
Jokanović Milan (University of Niš, Faculty of Medicine, Niš , Serbia)
Nikolić Goran M. (University of Niš, Faculty of Medicine, Niš , Serbia)

Ambroxol hydrochloride is an expectorant agent, successfully applied in mucolytic therapy for acute and chronic bronchopulmonary diseases. The drug regulates not only mucus secretion but also showed antioxidant, anti-inflammatory and local anesthetic properties. To supplement the pharmacokinetic and toxicological studies of ambroxol, a rapid ultra-high performance liquid chromatography-tandem mass spectrometry method for the quantitation of ambroxol in rabbit serum was developed. A validation of the method was performed as per the ICH guidelines for the validation of bioanalytical methods. The chromatographic separation was achieved in a submicron Kinetex RP - C18 - column (2.1 mm x 50 mm, 1.3μm) using the no buffer mobile phase. The ESI mass spectrometry in the MRM mode was used with a typical transitions m/z 378.9→263.8 for ambroxol and m/z 455.2→165.0 for IS. Linearity was determined with an average coefficient of determination >0.999 over the dynamic range from 0.5 - 200 ng/mL with LOD and LOQ of 0.25 ng/mL and 0.5 ng/mL, respectively. The results of the intra- and inter-day precision and accuracy determined in different days were all found to be within the acceptable limits ±15%. The present method was successfully applied to pharmacokinetic study in the rabbits after a single oral dose administration.

Keywords: ambroxol hydrochloride, UHPLC-MS/MS, serum, pharmacokinetics

Projekat Ministarstva nauke Republike Srbije, br. 175045