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Extractability-mediated stability bias and hematocrit impact: High extraction recovery is critical to feasibility of volumetric adsorptive microsampling (VAMS) in regulated bioanalysis.
J Pharm Biomed Anal. 2018 Jul 15; 156:58-66.JP

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.

Authors+Show Affiliations

Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA. Electronic address: yang_xu@merck.com.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.Merck Co. & Inc., Pharmacokinetics, Pharmacodynamics and Drug Metabolism, Regulated Bioanalysis, 770 Sumneytown Pike, WP75B-300, West Point, PA 19486, USA.

Pub Type(s)

Comparative Study
Journal Article
Validation Study

Language

eng

PubMed ID

29689469

Citation

Xie, Iris, et al. "Extractability-mediated Stability Bias and Hematocrit Impact: High Extraction Recovery Is Critical to Feasibility of Volumetric Adsorptive Microsampling (VAMS) in Regulated Bioanalysis." Journal of Pharmaceutical and Biomedical Analysis, vol. 156, 2018, pp. 58-66.
Xie I, Xu Y, Anderson M, et al. Extractability-mediated stability bias and hematocrit impact: High extraction recovery is critical to feasibility of volumetric adsorptive microsampling (VAMS) in regulated bioanalysis. J Pharm Biomed Anal. 2018;156:58-66.
Xie, I., Xu, Y., Anderson, M., Wang, M., Xue, L., Breidinger, S., Goykhman, D., Woolf, E. J., & Bateman, K. P. (2018). Extractability-mediated stability bias and hematocrit impact: High extraction recovery is critical to feasibility of volumetric adsorptive microsampling (VAMS) in regulated bioanalysis. Journal of Pharmaceutical and Biomedical Analysis, 156, 58-66. https://doi.org/10.1016/j.jpba.2018.04.001
Xie I, et al. Extractability-mediated Stability Bias and Hematocrit Impact: High Extraction Recovery Is Critical to Feasibility of Volumetric Adsorptive Microsampling (VAMS) in Regulated Bioanalysis. J Pharm Biomed Anal. 2018 Jul 15;156:58-66. PubMed PMID: 29689469.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Extractability-mediated stability bias and hematocrit impact: High extraction recovery is critical to feasibility of volumetric adsorptive microsampling (VAMS) in regulated bioanalysis. AU - Xie,Iris, AU - Xu,Yang, AU - Anderson,Melanie, AU - Wang,Ming, AU - Xue,Lingling, AU - Breidinger,Sheila, AU - Goykhman,Dina, AU - Woolf,Eric J, AU - Bateman,Kevin P, Y1 - 2018/04/05/ PY - 2018/01/29/received PY - 2018/04/02/revised PY - 2018/04/03/accepted PY - 2018/4/25/pubmed PY - 2018/10/12/medline PY - 2018/4/25/entrez KW - Extractability-mediated hematocrit effect KW - Extractability-mediated stability bias KW - Feasibility assessment KW - Recovery KW - Volumetric absorptive microsampling (VAMS) SP - 58 EP - 66 JF - Journal of pharmaceutical and biomedical analysis JO - J Pharm Biomed Anal VL - 156 N2 - 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. SN - 1873-264X UR - https://www.unboundmedicine.com/medline/citation/29689469/Extractability_mediated_stability_bias_and_hematocrit_impact:_High_extraction_recovery_is_critical_to_feasibility_of_volumetric_adsorptive_microsampling__VAMS__in_regulated_bioanalysis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0731-7085(18)30243-7 DB - PRIME DP - Unbound Medicine ER -