Analysis of Citalopram and Desmethylcitalopram in Postmortem Fluids and Tissues Using Liquid Chromatography-Mass Spectrometry

Citalopram is a selective serotonin reuptake inhibitor that is a commonly prescribed drug for the treatment of depression, obsessive-compulsive disorder, panic disorder, anxiety disorder, and post-traumatic stress disorder. While the use of citalopram is relatively safe, certain side effects could negatively affect a pilot’s performance and become a factor in an aviation accident. The side effects of this medication include nausea, tiredness, drowsiness, dizziness, and blurred vision. Due to the severity of aviation accidents, blood samples are often not available, so tissues must be relied upon for analysis. Therefore, understanding the distribution of a drug throughout postmortem fluids and tissues is important when trying to interpret drug impairment and/or intoxication. Our laboratory investigated the distribution of citalopram and its main active metabolite, desmethylcitalopram, in various postmortem tissues and fluids obtained from 15 fatal aviation accident cases. When available, 10 specimen types were analyzed for each case, including blood, urine, vitreous humor, liver, lung, kidney, spleen, muscle, heart, and brain. Whole blood citalopram concentrations obtained from these 15 cases ranged from 0.079 to 1.06 μg/mL. Distribution, expressed as specimen/blood ratio, for citalopram was 12 ± 19 in urine, 0.42 ± 0.21 in vitreous humor, 16 ± 8 in liver, 15 ± 15 in lung, 3.6 ± 2.5 in kidney, 8.1 ± 3.7 in spleen, 0.83 ± 0.40 in muscle, 2.3 ± 1.2 in brain, and 1.9 ± 1.0 in heart. Distribution coefficients obtained for citalopram had coefficient of variations (CV) ranging from 46-158%. With such large CV’s, the distribution coefficients have very little use in aiding in the interpretation of citalopram-positive tissue specimens. Furthermore, no consistent citalopram/desmethylcitalopram ratio was identified within any specimen group. This study suggests that citalopram likely undergoes postmortem concentration changes.