Simultaneous quantification of doxorubicin, lorazepam, metoclopramide, ondansetron, and ranitidine in mixtures by liquid chromatography-tandem mass spectrometry

A simple and rapid LC-MS/MS method for simultaneous quantification of a mixture of the antineoplastic agent doxorubicin (Dox) and selected emesis suppressants, namely, lorazepam (Lor), metoclopramide (Met), ondansetron (Ond), and ranitidine (Ran), was developed. 4-Phenyl-4-aminobutanoic acid was used as the internal standard (I.S.). The analytes were analyzed on an Xterra(TM) MS, C-18, 2.5 mum (2.1 mm x 30 mm) column using 70% aqueous methanol containing 0.1% formic acid. The investigated compounds were detected by tandem mass spectrometry (MS/MS) using a positive electrospray ionization mode. Multiple reaction monitoring transitions at m/z 544>361, 323>277, 301>228, 294>169, 315>176 and 180>163 (I.S.) were selected for simultaneous quantitation of Dox, Lot, Met, Ond, and Ran by an I.S. method. Calibration curves were constructed over the concentration ranges 10-200 ng mL(-1) (Dox, Lor), 8-80 ng mL(-1) (Ond), Met and Ran (1-10 ng mL(-1)). The coefficient of determination ranged from 0.9953 to 0.9998 with a limit of detection of similar to1 ng mL(-1) for all analytes. The overall percentage standard deviation and percentage deviation were <10% indicating good precision and accuracy. The developed LC-MS/MS method quantitatively recovered doxorubicin and the co-admixed compounds in the range 98.1%-103.5%. The data suggest the utility of the developed LC-MS/MS procedure for simultaneous routine analysis of mixtures of Dox and the emesis suppressants, Lor, Met, Ond, and Ran in I.V. infusions in clinics.