Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
7626284 | Journal of Pharmaceutical and Biomedical Analysis | 2018 | 9 Pages |
Abstract
Volumetric absorptive microsampling (VAMS), a new microsampling technique, was evaluated for its potential in supporting regulated bioanalysis. Our initial assessment with MK-0518 (raltegravir) using a direct extraction method resulted in 45-52% extraction recovery, significant hematocrit (Ht) related bias, and more importantly, unacceptable stability (>15% bias from nominal concentration) after 7-day storage. Our investigation suggested that the observed biases were not due to VAMS absorption, sampling techniques, lot-to-lot variability, matrix effect, and/or chemical stability of the compound, but rather the low extraction recovery. An effort to improve assay recovery led to a modified liquid-liquid extraction (LLE) method that demonstrated more consistent performance, minimal Ht impact (Ht ranged from 20 to 65%), and acceptable sample stability. The same strategy was successfully applied to another more hydrophilic model compound, MK-0431 (sitagliptin). These results suggest that the previously observed Ht effect and “instability” were in fact due to inconsistent extractability, and optimizing the extraction recovery to greater than 80% was critical to ensure VAMS performance. We recommend adding Ht-independent recovery as part of feasibility assessment to de-risk the long-term extractability-mediated stability bias before implementing VAMS in regulated bioanalysis.
Keywords
LLOQvolumetric absorptive microsamplingFDAVAMSULOQGLPEMALLELC–MS/MSEuropean Medicines agencyUS Food and Drug AdministrationFeasibility assessmentinternal standardLiquid–liquid extractionGood Laboratory Practiceupper limit of quantificationlower limit of quantificationRelative humidityRecoveryhematocrit%CVquality control
Related Topics
Physical Sciences and Engineering
Chemistry
Analytical Chemistry
Authors
Iris Xie, Yang Xu, Melanie Anderson, Ming Wang, Lingling Xue, Sheila Breidinger, Dina Goykhman, Eric J. Woolf, Kevin P. Bateman,