Biological Matrix Selection and Sample Collection
Selecting the Biological Matrix The choice of biological matrix is governed by the study objective, the physicochemical properties of the drug, and...
Selecting the Biological Matrix
The choice of biological matrix is governed by the study objective, the physicochemical properties of the drug, and applicable regulatory requirements. Plasma anticoagulated with ethylenediaminetetraacetic acid represents the most commonly employed matrix for pharmacokinetic and bioequivalence studies owing to its reproducible protein content and established stability characteristics, while heparinised plasma is preferred for certain enzyme-based assays. Whole blood is required for drugs exhibiting extensive partitioning into erythrocytes, reflected by a blood-to-plasma ratio exceeding unity, and increasingly supports dried blood spot sampling, which offers logistical advantages for remote and paediatric sampling. Urine provides high analyte concentrations suitable for renal excretion studies, cerebrospinal fluid enables assessment of central nervous system drug penetration, saliva offers a non-invasive matrix reflecting free drug concentration, and tissue homogenate and plasma ultrafiltrate serve specialised applications in distribution and protein-binding studies respectively.
Blank Matrix Procurement and Pre-Analytical Variables
Blank biological matrix, free from the analyte and internal standard, must be procured from a sufficient number of individual donors to support selectivity assessment during method validation, and its integrity must be confirmed prior to use. Pre-analytical variables represent the leading source of variability in bioanalytical data and must be rigorously controlled and documented, encompassing precise recording of collection time, the anticoagulant or additive employed, centrifugation conditions, processing temperature, the interval between collection and centrifugation, which should generally not exceed thirty minutes for labile compounds, and the number of freeze-thaw cycles to which the sample has been subjected prior to analysis.