Distribution of clomipramine, citalopram, midazolam, and metabolites in skeletal tissue after chronic dosing in rats

A fully validated method is presented and the distribution of clomipramine, citalopram, midazolam, and their major metabolites is examined within skeletal tissue of chronically dosed rats using LC −ESI−MS/MS. Clomipramine, citalopram, and metabolites, are shown to be detectable in all bone types sampled. Midazolam and its metabolite OH‐midazolam could not be detected. Within a rat, the drugs−metabolite ratio in the sampled bones is in close concordance to the ratios seen in blood. AbstractIn recent years, the use of skeletal tissue as an alternative matrix in forensic toxicology has received new interest. In cases where extreme decomposition has taken place, analysis of skeletal tissue is often the only option left. In this article, a fully validated method is presented and the distribution of clomipramine, citalopram, midazolam, and metabolites after chronically administration is examined within skeletal tissue. Rats were chronically dosed with respectively clomipramine, citalopram, or midazolam. Extracts were quantitatively analyzed using liquid chromatography −electrospray ionization−tandem mass spectrometry (LC−ESI−MS/MS). Clomipramine, citalopram, and metabolites, respectively desmethylclomipramine and desmethylcitalopram are shown to be detectable in all bone types sampled. Midazolam and its metabolite α‐OH‐midazolam could not be detected . The absence of midazolam in extracts gives an indication that drugs with pKa values under physiological pH are...
Source: Drug Testing and Analysis - Category: Drugs & Pharmacology Authors: Tags: RESEARCH ARTICLE Source Type: research