Pharmaceutical Perspectives of Use of Dried Blood Spots

Direct Analysis of Dried Blood Spot Samples

“…Numerous disadvantages to DBS sampling have been established, generally centred around concerns over sample volume, haematocrit, sample homogeneity, effects of temperature and humidity during transportation and storage, analyte recovery, filter paper characteristics, and anticoagulants (19,20,21,22) . Another key issue is the relationship between quantitatively measured analyte in dry (DBS) and wet (liquid whole blood or plasma) samples (23) .…”

“…In 2008 and 2009 Spooner and co-workers, at GlaxoSmithKline, published two articles on the use of dried blood spots (DBS) as a collection technique to support toxicokinetic and pharmacokinetic studies in pharmaceutical drug development that sparked a surge of interest in DBS in the pharmaceutical arena and beyond, which has continued to the present day (Figure 1.1) (25,26) . There are a number of reasons why, after being established as a concept for a century, DBS sampling suddenly became an interesting candidate for supporting quantitative drug bioanalysis (23) :…”

“…However, as more research was undertaken to underpin the science behind DBSs, a number of uncertainties arose, such as the homogeneity of DBS samples, the optimum method of adding IS and performing dilutions, the stability of aged DBSs, and most notably the impact of HCT on assay bias (19) . The FDA currently recommend that, until instructed otherwise, DBS data to support drug development studies should be run in parallel with conventionally used wet plasma or whole blood sampling (123,29,23) . It is assumed that the FDA will only recommend DBS data to be used in isolation once they have received, monitored and approved enough drug development studies for them to have sufficient confidence that the technique produces reliable and accurate data (123,29,23) .…”

“…However, recently the momentum behind introducing DBS analysis into highly regulated applications (such as pharmaceutical drug development) has hit a significant bottleneck due to a number of factors. The primary issues are uncertainty over regulatory acceptance, and scientific uncertainty over assay bias caused by varying haematocrit (HCT); while secondary issues include barriers to bioanalytical acceptance caused by the increased complexity of extraction, and lower assay sensitivity associated with DBS analysis (123,70,23) .…”

“…Note that it was initially envisioned that obtaining an accurate volume in the clinic by untrained (in bioanalysis) personal would be difficult to achieve with any confidence, and potentially expensive (accurate volume pipettes would have to be supplied to multiple clinical sites per study, calibrated, and the staff trained to use them). The requirement for accurate volume blood dispensing clearly compromises the simplicity of the original workflow that was envisioned for DBS, but the potential combined ethical, financial and logistic advantages on offer from DBS sampling still far outweigh the extra complexity and cost associated with an accurate volume DBS workflow, if practical accurate volume collection methods can be utilised (23,59) . In the last few years, new technology and whole blood dispensing techniques have been reported that potentially make accurate volume spotting, and whole-spot sample extraction options a realistic proposition (84,85,86,61,64,65,63) .…”