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

• Published in: Journal of pharmaceutical and biomedical analysis 2011-11, Vol.56 (3), p.577-581
• Main Authors: Nikolaou, Panagiota, Papoutsis, Ioannis, Athanaselis, Sotirios, Alevisopoulos, Giorgos, Khraiwesh, Alaa, Pistos, Constantinos, Spiliopoulou, Chara
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Biological and medical sciences; blood; Blood Chemical Analysis - methods; Calibration; Carbolines - blood; correlation; Derivatization; detection limit; Drug Monitoring - methods; drug therapy; Fundamental and applied biological sciences. Psychology; gas chromatography; Gas Chromatography-Mass Spectrometry - methods; GC/MS; General pharmacology; Humans; hypertension; mass spectrometry; Medical sciences; monitoring; pharmacokinetics; Pharmacology. Drug treatments; Phosphodiesterase 5 Inhibitors - blood; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction - methods; Solid-phase extraction; Tadalafil; Whole blood
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2011.05.036

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 2.00μg/L, respectively. The calibration curve was linear between 2.00 and 500.0μg/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.