Abstract

DERIVATIZED DETECTION BY TANDEM MASS SPECTROMETRY AND PHARMACOKINETICS OF RISEDRONIC ACID IN HUMAN VOLUNTEERS

Ch. Venkata Kumar* and Naga Malleswara Rao K

ABSTRACT

Pharmacokinetic studies are essential towards determining bioequivalence and establishing pharmacokinetic profiles for drug moieties requires accurate quantification. We have developed and validated a rapid, sensitive and robust liquid chromatography with tandem mass spectrometric method for the determination of risedronic acid in human plasma as per regulatory guidelines. Deuterated compound of risedronic acid was used as an internal standard. The chromatographic separation was achieved by X Bridge, Bisphosphonate C18 column using isocratic mobile phase consists a mixture of 5 milli molar ammonium acetate and acetonitrile (5:95 v/v) over a run time of 4.0 minutes. An aliquot of 200 μL of human plasma was used for the extraction of the drug by using solid-phase extraction technique. The transition (m/z) of molecular ion Q1 to product ion Q3 for risedronic acid was found to be 340.2→214.0. The proposed method was validated in the concentration range of 0.100 - 50.070ng/mL with positive polarity ionization mode in multiple reaction monitoring (MRM). The pharmacokinetic parameters for Risedronic acid were found to be Tmax – 1.13 Hours, Cmax – 21.1 ng/mL, T1/2 – 20.4 Hours, AUC (0-72) 77.6 ng.Hrs/mL and AUC (0-inf) 80.3 ng.Hrs/mL. The proposed assay method was found to be acceptable to a pharmacokinetic study in human volunteers.

Keywords: Derivatization, Risedronic acid, Plasma, Solid Phage Extraction and LCMS/ MS.