Direct multiclass desorption electrospray ionization-tandem mass spectrometry method for the analysis of sleep inducers and ototoxic drugs in dried blood spots.

RATIONALE: An unconventional and innovative approach for the quantitative determination of 11 ototoxic and narcoleptic drugs in whole blood is described. The multiclass method allows the inclusion of the most widespread drugs on the market (antihistamines, antidepressants, antihypertensives, anxiolytics, opioids, Z-drugs) responsible for 10% of occupational accidents. METHODS: The developed procedure involved the use of the desorption electrospray ionization (DESI) interface for the direct analysis of dried blood spots (DBS). All the issues strictly connected to the chemical-physical characteristics of DBS and DESI (sample inhomogeneity, DBS support, DESI geometry and solvent) were carefully evaluated and innovative strategies were applied. Haematocrit was managed using a small and measured volume of blood (2 µL) with analysis of the entire DBS. RESULTS: The proposed method was fully validated in terms of limits of detection, limits of quantitation (LOQs; between 60 pg/mm2 and 1.6 ng/mm2 ), linearity (one order of magnitude starting from LOQs) and inter- and intra-day precision (on three levels, with relative standard deviation values not exceeding 17%). Accuracy was calculated by comparison with an ultrahigh-performance liquid chromatography-tandem mass spectrometry method (suitable also as a confirmatory method). CONCLUSIONS: Results showed a surprising sensitivity, demonstrating that this procedure could be suitable for applications in various fields, e.g. forensic analysis. Moreover, as a collateral benefit, it was discovered that the method is able to analyse very light traces left on plastic and glass surfaces by detached dried blood.

A 'Dilute and Shoot' Liquid Chromatography-Mass Spectrometry Method for Multiclass Drug Analysis in Pre-Cut Dried Blood Spots.

Drugs able to affect the auditory and nervous systems and consumed by workers to treatdifferent pathologies can represent a possible source of risk in the work environment. All the target compounds involved in the presented project show ototoxic and/or narcoleptic side effects and, for these reasons, occupational safety organizations have recognized them as potential causes of work injuries. A multiclass method for the analysis of 15 drugs among the most widespread worldwide (belonging to nine different classes including antihistamines, beta-blockers, antidepressants, Z-drugs and opioids), was developed and validated. This study describes a rapid, sensitive and effective method to analyse these substances in whole blood using tailored pre-cut dried blood spots. Detection was achieved with a triple quadrupole mass spectrometer after an easy and simple 'dilute and shoot' solubilisation followed by an UPLC separation. All the issues linked to the use of the dried blood spots and whole blood, such as haematocrit variability, volumetric evaluation and sample carrier choice were carefully studied and managed during method development. From the validation study results it emerged that this approach can be deemed successful thanks to its few pg µL-1 LOQs, good linear intervals, absolute recoveries of no less than 75%, an almost negligible matrix effect and accuracy and precision in line with the European and American guidelines for validation. All the obtained goals have been specifically pursued in order to encourage method diffusion as a primary prevention intervention, even in small private workplaces.