EUROMEDICA  Hanover 1-2  Juni 2007	Advanced methods of diagnosis, treatment and prophylactics
	European Academy of Natural Sciences, Hanover European Scientific Society, Hanover Russian Academy of Natural Sciences, Moscow

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Therapeutic drug monitoring (TDM) of cardiovascular drugs such as non-selective beta and calcium channel blockers has been introduced for optimization of pharmacotherapy. Carvedilol, propranolol and amlodipine are commonly prescribed for treatment of cardiovascular diseases. However, no previous investigation of three drugs has been conducted by high performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-MS/ESI). OBJECTIVE: to establish a new, rapid and sensitive HPLC-MS/ESI method for simultaneous determination and screening three common cardiac medications carvedilol, propranolol and amlodipine in human plasma.

METHODS: The analytes in plasma were extracted by solid-phase-extraction column after samples had been alkalinized. Solid-phase extraction of these drugs added to the human plasma was performed with an Oasis HLB cartridge column. The HPLC separation of the analytes was performed on a Zorbax 300 SB-C18 (100 mm x 2.1 mm, 3.5 mcm) column, using water (formic acid 1 per thousand)-acetonitrile (35:65, v/v) as a mobile phase, with a flow-rate of 0.40 ml/min. The compounds were ionized in the electrospray ionization (ESI) ion source of the mass spectrometer and were detected in the multiple reaction monitoring (MRM) mode. MRM using precursor-->product ion combinations at m/z 409-->238, 407-->100 and 260-->115 was applied to determine amlodipine, carvedilol and propranolol, respectively

RESULTS: The calibration curves were linear in the 10-1000 ng/ml range for all compounds, all of them with coefficients of determination above 0.98. The average extraction recoveries for all four analytes were above 75%. The methodology recoveries were higher than 95.0%. The limits of detection (LODs) were 5, 3 and 3 ng/ml for carvedilol, propranolol, and amlodipine, respectively. The intra- and inter-day variation coefficients were less than 15.0%. CONCLUSION: The method is accurate, sensitive and simple for routine TDM as well as toxicological screening, and for the study of pharmacokinetics and metabolism of three drugs.