Development and validation of a GC/MS method for the determination of tadalafil in whole blood.

Tadalafil is a phosphodiesterase type 5 (PDE-5) inhibitor and it is used in the treatment of pulmonary arterial hypertension and erectile dysfunction. A sensitive and specific method is described for the determination of tadalafil in whole blood. Tadalafil and its internal standard (protriptyline) were isolated from the matrix by solid phase extraction, and were analyzed by gas chromatography/mass spectrometry (GC/MS) after derivatization by N,O-bis(trimethylsilyl)-trifluoracetamide (BSTFA) with 1% trimethylchlorsilane (TMCS). Limits of detection and quantification for tadalafil were 0.70 and 2.00 μg/L, respectively. The calibration curve was linear between 2.00 and 500.0 μg/L, with a correlation coefficient higher than 0.991. The values obtained for intra- and inter-day accuracy was found to be between -10.5 to 8.5% and -4.2 to 4.5%, respectively, while intra- and inter-day precision were less than 8.4 and 11.2%, correspondingly. Absolute recovery was determined at three concentration levels and ranged from 92.1 to 98.9%. The proposed method is the first fully validated GC/MS method for the determination of tadalafil in whole blood and it can be routinely applied by toxicological laboratories, for pharmacokinetic studies, for therapeutic drug level monitoring or for the investigation of related forensic cases.