Identification and quantitative determination of xenobiotics in hair by new, higly specific mass spectrometry approaches

The analysis of drugs in hair samples has become very popular in recent years with possible applications in forensic and in clinical toxicology. Hair testing can complement conventional blood and urine analysis as it enlarges the window of detection and, by segmentation, permits differentiation between long-term therapeutic use and single exposure. The use of high specific and sensitive analytical procedures is therefore required to achieve low limits of detection. In this study new analytical procedures were developed for the accurate and specific quantification of xenobiotics whose determination in hair would be of toxicological or forensic interest. The research program was developed into three phases. In the first one a new selective and sensitive method, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS), was developed and validated for the quantitative determination in hair of ergotamine, a highly toxic drug, used to treat vascular headaches. The validated method was successfully applied to a case of iatrogenic ergotism resulting from the prolonged intake of ergotamine tartrate for recurrent headaches. The second phase consisted of the development and validation of a new LC-MS/MS method for the assay of citalopram and escitalopram, two highly selective serotonine reuptake inhibitors, used for the treatment of depression and anxiety disorders, and their demethylated metabolites, in 10-mg hair samples: This method proved suitable for neonatal hair analysis and was applied to two real cases of gestational exposure to the drugs. In the third phase, a fast screening method, based on matrix-assisted laser desorption/ionization (MALDI) mass spectrometry was developed for the detection of cocaine and its metabolites, benzoylecgonine and cocaethylene, in hair samples. Different MALDI sample preparation approaches have been tested and the employment of a multi-layer procedure yielded the best results for standard solutions of the target analytes; the same approach was subsequently applied to hair samples that were known to contain cocaine and metabolites, as determined by a classical gas chromatography-mass spectrometry (GC-MS) method.