Dried Blood Spot Sampling: Coupling Bioanalytical Feasibility, Blood–Plasma Partitioning and Transferability to In Vivo Preclinical Studies

Abstract

Transition from plasma to DBS can be supported for preclinical studies by conducting a few well-defined bioanalytical experiments followed by an in vivo bridging study. Blood:plasma ratio derived from the bridging study can be used to predict plasma concentrations from DBS data.

A First-in-Human Phase 1 Study of LY3023414, an Oral PI3K/mTOR Dual Inhibitor, in Patients with Advanced Cancer

“…Venous blood was drawn at each time point and collected using the dried blood spot (DBS) sampling technique (10,11). LY3023414 concentrations were quantitated using a validated LC/MS-MS method with a range spanning from 2 ng/mL to 1,000 ng/mL.…”

Automated Direct Extraction and Analysis of Dried Blood Spots Employing On-Line SPE High-Resolution Accurate Mass Bioanalysis

“…DBS techniques have been widely used since the 1960s for neonatal screening of inherited metabolic disorders [8,9], and recently, the use of DBS has been greatly increased by the enhanced sensitivity and selectivity offered by LC-MS, an important factor for the measurement of drugs from DBS obtained from few microliters of blood [10][11][12]. As a result, numerous bio-analytical applications have demonstrated the utility of DBS in pharmacokinetic and toxicokinetic studies, therapeutic drug monitoring and drug discovery [13][14][15][16][17].…”

Assessment of The Within- and Between-Lot Variability of Whatman™ Fta ® DMPK and 903 ® DBS Papers and Their Suitability for The Quantitative Bioanalysis of Small Molecules

“…Control human blood containing K3 EDTA was supplied by GlaxoS-mithKline (GSK) volunteers in accordance with current GSK policies on informed consent and ethical approval and used on the day of collection. Compounds used as analytes during the study and their IS were sourced as follows: ibuprofen (IB), 2 H 3 IB, paracetamol (PC) and proguanil (PG) were obtained from Sigma-Aldrich (Pool, UK), 2 and solvents were either purchased from Fisher Scientific, Sigma-Aldrich or were prepared inhouse at GSK. All solvents were of HPLC grade and chemicals of AnalaR grade.…”

“…Recently, there has been a notable increase in interest in the use of this sample collection technique for the quantitative determination of drugs in preclinical and clinical drug development studies and therapeutic drug monitoring [2][3][4][5][6][7][8][9][10][11]. This is due to a number of advantages of the technique compared with conventional whole blood and plasma sampling.…”