Comparative LC-MS and HPLC analyses of selected antiepileptics and beta-blocking drugs

A highly sensitive and specific assay procedure based on the combination of liquid chromatography and mass spectrometry (LC-MS) has been developed for the quantitative analysis of selected antiepileptics (carbamazepine and ph enytoin) and beta-blocking drugs (acebutolol, atenolol, pindolol and propra nolol) using APCI as an ionization process. The measured concentration rang e was 100-300 ng ml(-1) for all drugs except phenytoin (0.5-1.5 mu g ml(-1) ). Analysis was based on direct injection of methanolic solutions of drugs into the mass spectrometer with the subsequent elution with a mobile phase consisting of methanol and 1% acetic acid solution (4:1) at a flow rate 1 m i min(-1). The mass spectrometer was programmed to permit detection and det ermination of either fragment or molecular ions of carbamazepine, phenytoin , acebutolol, atenolol, pindolol and propranolol at m/e 194.3, 252.9, 337.2 , 267.1, 249.1 and 260.1, respectively. The recorded chromatograms exhibite d well-resolved peaks at retention times < 1 min. The peak area was correla ted linearly to the drug concentration. Intraday precision gave relative st andard deviations in the range 1.75-4.02%. Compared to HPLC, the described LC-MS was faster, more sensitive and specific. Unlike HPLC, LC-MS could be applied to analyze incompletely resolved mixtures. The absolute detection l imits for LC-MS and HPLC were 0.2-0.5 and 10-25 ng, respectively. Recovery studies of the investigated compounds in pharmaceutical products using LC-M S and HPLC gave mean percentages of 97.5-102.0 and 98.4-103.3, respectively . Statistical analysis of the data using t- and F-tests showed insignifican t differences between both methods for the analysis of carbamazepine, pheny toin, acebutolol and atenolol in pharmaceutical formulations. However, LC-M S gave more accurate results than HPLC for determination of pindolol in tab lets. Propranolol could only be determined in tablets using LC-MS. (C) 2000 Elsevier Science S.A. All rights reserved.