Opening the toolbox of alternative sampling strategies in clinical routine: A key-role for (LC-)MS/MS

Abstract

Alternative sampling strategies such as dried blood sampling, liquid microsampling and the sampling of oral fluid, hair, meconium, interstitial fluid, sweat, exhaled breath condensate and sputum offer interesting opportunities for many applications in clinical routine. Here, we provide an overview of different applications, with special attention to the pivotal role of LC-MS/MS in facilitating analysis of the collected matrices. Covered clinical fields include newborn screening, endocrinology, therapeutic drug monitoring, phenotyping, toxicology, proteomics and metabolomics. Furthermore, specific advantages, challenges and limitations of each alternative sampling strategy are discussed, along with recent advances and future trends that may contribute to routine implementation of these sampling strategies. Given the development of many recent potentially valuable clinical applications, the possibility of home sampling and the opportunity to obtain information that is hard to procure using traditional sampling, a well-balanced role for alternative sampling strategies can be envisaged in patient healthcare in the (near) future.

Dried blood spots in therapeutic drug monitoring and toxicology

“…DBS-based TDM has been reported for various therapeutic drug classes, including anticonvulsants, antiretrovirals, immunosuppressants, antimalarials, antibiotics, analgetics, antidepressants, etc. [4][5][6]12]. Also (bio)markers such as HbA1c can be followed up via dried blood microsamples [15].…”

“…Also (bio)markers such as HbA1c can be followed up via dried blood microsamples [15]. However, it needs to be mentioned that routine implementation in clinical laboratories has remained limited so far [12]. The small amount of sample mostly requires very selective and sensitive instrumentation (e.g.…”

“…The development of fully automated DBS analyzers that can be directly coupled to standard LC-MS/MS configurations is essential for routine laboratories focusing on highthroughput assays. In these systems, solvents elute a fixed area from a DBS card, obviating the punching step, after which the extract is directed to an online sample clean-up and/or separated on an LC column, or even directly injected into the MS. By built-in accessories, such as, for example, barcode readers, these automated systems eliminate human errors associated with manual handling, allowing sample registration and traceability [12].…”

“…These systems may be equipped with tools for automated recognition of correctly deposited DBS and for coping with variables like hct, for example, via the integration of reflectance spectroscopy for hct prediction [11]. This tailoring to current (and future) workflows of routine clinical laboratories, focusing on highthroughput, is essential for more widespread implementation [12].…”

“…New sampling devices are entering the market, automated analysis leads to a higher efficiency, sample throughput and reproducibility and different strategies to cope with the hct effect have been put forward [10,11]. Innovations include whole-spot analysis of volumetrically applied DBS, development of alternative dried blood sampling devices, introduction of special types of filter paper, as well as cards for generating dried plasma spots, and setup of approaches for hct prediction of DBS, allowing the correction of hct-skewed results [11,12].…”