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

Abstract

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 phenytoin) and beta-blocking drugs (acebutolol, atenolol, pindolol and propranolol) using APCI as an ionization process. The measured concentration range was 100–300 ng ml −1 for all drugs except phenytoin (0.5–1.5 μg 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 ml min −1. The mass spectrometer was programmed to permit detection and determination 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 exhibited well-resolved peaks at retention times <1 min. The peak area was correlated linearly to the drug concentration. Intraday precision gave relative standard 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 limits 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–MS 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 insignificant differences between both methods for the analysis of carbamazepine, phenytoin, acebutolol and atenolol in pharmaceutical formulations. However, LC–MS gave more accurate results than HPLC for determination of pindolol in tablets. Propranolol could only be determined in tablets using LC–MS.