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

Abstract

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.

Applications of ambient ionization mass spectrometry in 2022: An annual review

“…In terms of sample storage, the technique offers similar advantages to the use of dried blood spots, though in this study samples were only evaluated after storage for several days, far short of the several months that samples would likely be stored for monitoring during spaceflight. In a recent study by Rocca et al., a DESI‐MS method was developed for the detection and quantification of 11 ototoxic and narcoleptic drugs in dried blood spots 116 . Using an automated system to locate and ionize lines of multiple samples and replicates, the technique demonstrated the ability to rapidly target and detect multiple classes of drugs with high precision and accuracy in comparison to a standard LC‐MS/MS method.…”

“…In a recent study by Rocca et al., a DESI‐MS method was developed for the detection and quantification of 11 ototoxic and narcoleptic drugs in dried blood spots. 116 Using an automated system to locate and ionize lines of multiple samples and replicates, the technique demonstrated the ability to rapidly target and detect multiple classes of drugs with high precision and accuracy in comparison to a standard LC‐MS/MS method. PS‐MS has also been used for the detection of pharmaceuticals in biological fluids, being used for the detection of remdesivir and its active metabolite in plasma 117 and coupled with a miniature MS for the detection of HIV drugs in whole blood.…”

Potential of desorption electrospray ionization and paper spray ionization with high-resolution mass spectrometry for the screening of sports doping agents in urine

“…These techniques have been proposed for the analysis of different families of drugs in complex biological fluids such as urine and blood, mainly in pharmacology and forensic applications. 8,13–35 In the field of doping control, DESI has been used for the analysis of clenbuterol in urine pretreated with solid phase extraction 26 and for the analysis of anabolic steroids in urine by reactive DESI. 22 PSI has been applied to the analysis and/or quantitation of a couple of stimulants, 13,21 a combination of two steroids and two diuretics 18 and a limited number of very polar compounds.…”