Citalopram and escitalopram in hair segments from deceased individuals with mental illnesses

To aim of the study was determine concentrations of citalopram, escitalopram and their primary metabolite in hair segments from individuals with mental illnesses and correlate them to an estimated daily dose. Citalopram is a commonly sold antidepressant. It contains a chiral center and is used in therapy as the racemic mixture (RS-citalopram) or as the pure enantiomer (S-citalopram), escitalopram. The use of pharmaceuticals, polypharmacy and drug abuse can all been linked to elevated death rate among individuals with mental illnesses. Therefore, information on previous drug intake is important and can be obtained by hair analysis. Monthly drug intake before death is investigated using an average hair growth rate of 1 cm/month and analysis of 1 cm hair segments. Investigations on drug distribution in the hair and its relationship to the estimated dose provide insight into the interpretation of forensic cases. Hair samples were collected from 44 deceased individuals included in the autopsy-based study “SURVIVE” and had a presumed history of citalopram use based on results in the postmortem blood sample or the case history. Citalopram and N-demethylcitalopram were quantified using a previous method optimized to cover long-term drug intake. The method was successfully validated according to international guidelines with a measurement range of 0.005 to 100 ng/mg by using 12 C and 13 C isotopes. Depending on the length of the hair, hair samples were cut into 6 × 1 cm segments corresponding to six months before death. The segments were weighted, washed, pulverized, and incubated over night at 37 °C in an extraction medium of methanol, acetonitrile and 2 mM ammonium formate (25:29:46, v/v/v). After filtration, the extract was injected into an LC–MS/MS system. Soaked QCs in hair at three concentrations levels were included. After quantification, R- and S-citalopram were identified using a method adapted from chiral determination of citalopram in blood. Prescription data was used to estimate daily doses. We found citalopram concentrations in hair ranging from 0.12 to 67 ng/mg (10th–90th percentile) with a median of 8.2 ng/mg (N = 40 individuals, n= 182 segments) and escitalopram concentrations ranging from 0.027 to 7.0 ng/mg (10th–90th percentile) with a median of 3.9 ng/mg (N = 4, n = 23). Similar or decreasing concentrations throughout the segments were often detected, indicating a probable wash out of citalopram over time. The daily doses calculated varied from 1.3 to 69 mg/day (median 27 mg/day). We found no correlations between the hair concentrations and the estimated daily dose (N = 30, P = 0.1). However, after accounting for the calculated daily doses, our findings revealed a propensity for dark hair to have higher citalopram concentrations than light hair, indicating a possible effect of hair color on the hair concentration. The 10th–90th percentile metabolite-to-drug ratios in hair were 0.053–0.63 (N = 39, n = 166) with intraindividual variability of <25% for most individuals. Citalopram concentrations >30 ng/mg were found in 13 individuals suggesting very high levels in hair. The chiral analysis revealed that racemic citalopram had a median R/S ratio of 1.5 (N = 27), which is consistent with blood ratios. This study determined concentrations of citalopram, escitalopram and N-demethylcitalopram in 1 cm segments from 44 deceased individuals with mental illnesses applying chiral separation of R- and S-citalopram. This is the first study reporting chiral separation of citalopram in hair samples. No correlations were found between the concentrations in hair and the estimated daily dose. However, our findings suggest that hair color has an impact on this. This research contributes to the establishment of reference values for citalopram in hair for future forensic investigations.