A fully validated method for the simultaneous determination of 11 antidepressant drugs in whole blood by gas chromatography–mass spectrometry

• Published in: Journal of pharmaceutical and biomedical analysis 2012-11, Vol.70, p.557-562
• Main Authors: Papoutsis, Ioannis, Khraiwesh, Alaa, Nikolaou, Panagiota, Pistos, Constantinos, Spiliopoulou, Chara, Athanaselis, Sotirios
• Format: Article
• Language: English
• Subjects: Analysis; Analytical, structural and metabolic biochemistry; Antidepressants; Antidepressive Agents - blood; Antidepressive Agents - pharmacokinetics; Biological and medical sciences; Biotransformation; blood; Calibration; derivatization; Drug Monitoring - methods; Fluorocarbons - chemistry; Forensic Toxicology - methods; Fundamental and applied biological sciences. Psychology; Gas chromatography; Gas Chromatography-Mass Spectrometry - standards; gas-chromatography-mass spectrometry; General pharmacology; Humans; Limit of Detection; Linear Models; Mass spectrometry; Medical sciences; metabolites; Pharmacology. Drug treatments; Reference Standards; Reproducibility of Results; Sensitivity and Specificity; Solid Phase Extraction; Whole blood
• ISSN: 0731-7085; 1873-264X
• DOI: 10.1016/j.jpba.2012.05.007

Antidepressant drugs are widely used for the treatment of depression and other psychiatric disorders and as a result they are involved in numerous clinical and forensic cases. The aim of this study was the development, optimization and validation of a simple, specific and sensitive GC/MS method for the simultaneous determination of 11 antidepressant drugs and 4 of their metabolites (amitriptyline, citalopram, clomipramine, fluoxetine, fluvoxamine, maprotiline, desmethyl-maprotiline, mirtazapine, desmethyl-mirtazapine, nortriptyline, paroxetine, sertraline, desmethyl-sertraline, venlafaxine and desmethyl-venlafaxine) in whole blood. The combination of solid-phase extraction with derivatization using heptafluorobutyric anhydride efficiently reduced matrix effect and improved sensitivity of the method. In this assay, protriptyline was used as internal standard. Absolute recovery values for all analytes were ranged from 79.2 to 102.6%. LODs and LOQs were found to be between 0.30–1.50μg/L and 1.00–5.00μg/L, respectively. The calibration curves were linear (R2≥0.990) within the range of 5.00–1000μg/L for all analytes. Accuracy expressed as the % Er was found to be between −12.3 and 12.2%. Precision expressed as the % RSD was found to be less than 11.7% for all antidepressants. The developed method proved to be suitable for routine work and it was used to successfully analyze more than 2500 clinical and forensic blood samples.