Quantification of Imipramine, Amitriptyline and their Major Metabolites in Urine Samples of Depressed Patients by Gas Chromatography-Mass Spectrometry

Abstract

Biotransformation of antidepressant drugs is said to affect their pharmacological profile and subsequently alter their treatment efficacies. Imipramine and amitriptyline are the major drugs used for the management of manic depression at the Ankaful psychiatric hospital in Ghana. Recent reports have shown that some patients stay longer on this therapy than expected, while others do not get well at all. Herein, we report a modified solid phase extraction (SPE) method for the extraction of these antidepressant drugs; imipramine, amitriptyline and their respective metabolites, desipramine and 10-hydroxyamitriptyline from urine samples of five adult manic depressed patients. The compounds were simultaneously analyzed by gas chromatography-mass spectrometry (GC-MS). The calibration curves were linear over a range of 10-100 µg/L for all the analytes with the square of the regression coefficient (R2) ranging from 0.990 to 0.997. Analyses of the drugs and their respective metabolites over a 40 day period gave an average of 3.65 µg/L 10-hydroxyamitriptyline with negligible levels of amitriptyline. An average of 27.01 µg/L desipramine was also recorded against 10.30 µg/L of imipramine. These high levels of metabolites and relatively low amounts of the parent drugs recorded in the urine samples could be the main cause of the patients staying longer on the therapy and the resultant abscondment of one of them.