Editorial Spooner
are comparable to established approaches [11]. The sim- plicity of the paper based system with a colorimetric out- put enables bedside and off-site measurements for dia- betic patients to be made in resource-limited and remote locations. Other manuscripts built on this and specu- lated about the benefits and hurdles to development and implementation of such devices in the future [12,13]. An alternative approach that can be used for in vivo
extraction of the analyte of interest was introduced by Donabella and co-workers [14]. Their supported liquid- phase microextraction probes can be inserted directly into blood vessels and tissues and were successfully used to monitor the PK of oxybutynin in rabbits without the need to withdraw a blood sample.
Increased understanding of the technologies DBS sampling technologies still formed the majority of all the microsampling publications in the journal in 2015. Investigators are increasing our understand- ing of this important technology by exploring differ- ent aspects of the devices and workflows to ensure that the technologies are being used appropriately and the q uality of data is understood and maximized. Koster and colleagues explored different approaches
to preparing blood with different hematocrit values in order to perform validation experiments to under- stand the impact of this parameter on bioanalytical assays when DBS sampling is used [15]. Further work by Koster and colleagues investigated DBS sampling on five different cards and concluded that the cards performed differently, particularly at extreme concen- trations and hematocrit values [16]. The outcome of which is that they recommend an investigation of the different types of DBS cards prior to validation of the bioanalytical method. Another manuscript by Koster and co-workers found a relationship between the number of hydrogen-bond acceptors and the recovery of immunosuppressants from DBS samples [17]. The higher the number of hydrogen-bond a cceptors, the lower the recovery. The effect of drying on homogeneity of DBS sam-
ples was investigated by Lenk and colleagues, who recommended that this parameter should be inves- tigated as part of bioanalytical method development and validation [18].
Workflow process improvement Several manuscripts have outlined the use of micro- sampling for drug discovery PK in rodents. Korfm- acher and colleagues outlined a routine approach for the collection of serial 8 µl whole blood microsamples from single mice and demonstrated good concordance with concentrations determined in blood and plasma samples collected by conventional means for either,
Bioanalysis (2016)
single-, or multi-day studies [19]. Takyi-Williams and co-workers published a manuscript outlining the use of paper spray-MS to simplify workflows in nonclini- cal PK drug discovery studies [20]. Using a 2 µl plasma aliquot derived from a 20 µl blood sample, the inves- tigators were able to generate 8 sample full PK profiles in a single mouse. Furthermore, their approach does not require sample preparation, or chromatography, and delivers turnaround times of less than 1 min per sample. A number of manuscripts have investigated enhanced
workflows for the direct and efficient analysis of DBS samples. An approach for direct elution of DBS sam- ples and optimizing the performance for high through- put analysis demonstrated that assay sensitivity could be increased by up to 33 fold compared with generic conventional manual extraction of DBS samples [21]. Another approach using heated flow-through desorp- tion demonstrated hematocrit-independent recovery of immunosuppressants [22].
Applications A number of laboratories are now demonstrating the routine use of a variety of microsampling approaches for the determination of TK and PK in preclinical studies in a variety of species [5,14,19,20,23], enabling the generation of high-quality exposure data, while deliv- ering the ethical benefits of reduced blood sampling volumes. A variety of publications have demonstrated the
applicability of microsampling, and specifically dried matrix spot (blood, plasma, urine or cerebrospinal fluid)
sampling, for routine and high-quality bio-
analytical determinations of a variety of analytes in humans, including drugs and biomarkers [24-32]. A number of the studies have shown good correlation between PK data obtained from microsampling and that obtained by conventional approaches. The micro- sampling approach to sample collection and analysis is now being regularly employed to generate high-quality data for therapeutic drug monitoring of a wide vari- ety of analytes, and diseases. Further, the use of these approaches may have an important role for increas- ingly over-burdened healthcare systems [33], for drugs of abuse monitoring [34] and for screening of newborns and pregnant women for lead [35]. A manuscript by Déglon and co-authors presented
an in-depth discussion and perspective on the history of dried matrix sampling for biomedical use and the associated ‘hype cycle’. This has seen this technique go from early adoption, through the ‘peak of inflated expectations’ followed by the ‘trough of disillusion- ment’, associated with the issues around hematocrit and homogeneity for DBS sampling [36]. Further inves-
future science group
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