A Novel Approach to Capillary Plasma Microsampling for Quantitative Bioanalysis

Abstract

A simple and robust novel approach for the collection of small plasma volumes from rodent TK studies has been demonstrated.

Evaluation of plasma microsampling for dried plasma spots (DPS) in quantitative LC-MS/MS bioanalysis using ritonavir as a model compound

“…Three validation core runs along with other assessments were conducted according to the current health authority guidance on bioanalytical method validation [7,8] and LC-MS/MS bioanalytical practice [1,[3][4][5][6] to evaluate the precision and accuracy of the assay method using DMPK C cards. Each core validation batch was processed on a separate day and had two replicates of each calibration standard and six replicates of each QC sample at concentrations of 50.0, 150, 300 and 3750 ng/mL.…”

“…Briefly, <100 L blood sample is collected into a microsampling capillary or plastic device which is then centrifuged. The harvested plasma samples, which are the same as conventional wet plasma, can be directly analyzed [2,3]. However, since the technique deals with a small plasma volume (generally <30 L), there is a concern that the harvested plasma may not be sufficient for multiple analyses (initial analysis, repeat analyses in duplicate and incurred sample reanalysis) using standard pipetting (typically ≥10 L).…”

“…A plasma microsampling technique is currently on the horizon for quantitative bioanalysis in support of drug development [1][2][3]. Briefly, <100 L blood sample is collected into a microsampling capillary or plastic device which is then centrifuged.…”

Direct Analysis of Dried Blood Spot Samples

“…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) . New blood collection technologies such as the DBS-System (from Déglon et al), and Mitra or volumeric absorptive microsampling (VAMS) (from Phenomenex, albeit in a different format to card based DBS) demonstrate that practical, and cost effective solutions to accurate volume blood microsampling are available (63,130) .…”

Evaluation and Optimization of Blood Micro-Sampling Methods: Serial Sampling in a Cross-Over Design from an Individual Mouse

“…In addition, the adoption of various bleeding techniques to enable micro-sampling of blood or plasma (generally defined as the collection of blood volumes of less than 50 µL) has enabled the collection of multiple PK time points and the generation of a complete PK profile from a single mouse. These techniques include micro-sampling of plasma either as liquid plasma (8)(9)(10), or as dried plasma spots (11), and micro-sampling of blood either as liquid blood (12)(13)(14)(15), or as dried blood spots (DBS) (2)(3)(4)(16)(17)(18). Overall, micro-sampling also benefits the adoption and compliance with the 3Rs principles (Reduction, Refinement, and Replacement in animal usage) (19).…”