Stabilization of Clinical Samples Collected for Quantitative Bioanalysis – A Reflection from The European Bioanalysis Forum

Abstract

In bioanalysis of small molecules, the analyte concentration in the measured samples should reflect the concentration during sample collection. Precautions may be needed to prevent over- or under-estimation of the obtained result. This might require the addition of stabilizers to prevent degradation or nonspecific binding. For unstable drugs, it is essential to know how analytes can be stabilized before the start of the clinical study. Although the stabilization methods are well documented, the impact of the stabilization on the clinical workflow is not properly addressed. Already during method development, the clinical implications in terms of personnel safety, ease of use, training possibilities and staff capacity should be taken into account, and validation of the bioanalytical method should reflect collection procedures.

Clinical Evaluation Based on a New Approach to Improve the Accuracy of 4β-Hydroxycholesterol Measurement as a Biomarker of CYP3A4 Activity

“…The ICH M10 guidelines [ 21 ] require that plasma NCEs and their metabolites are measured in clinical trials using appropriate protocols. To accurately measure NCEs and metabolites in accordance with these guidelines, plasma collected with various anticoagulants is often stabilized under acidic conditions to prevent artificial (ex vivo) conversions (e.g., metabolites of NCEs, such as acyl glucuronides, lose their glucuronic acid groups when plasma is stored under neutral conditions) during storage [ 10 , 11 ]; however, little is known about the effects of these anticoagulants, or plasma acidification, on the measurement of 4β-HC. Previous reports are limited to examining the stability of 4β-HC in plasma collected with K2-EDTA or in serum [ 12 , 13 , 14 , 15 ]; thus, we considered it necessary to evaluate the effects of various anticoagulants and plasma acidification on the measurement of 4β-HC under different plasma storage conditions.…”

“…Factors that may hinder accurate analysis include plasma collection conditions and storage conditions [ 9 ]. From this perspective, the acidification of plasma (obtained using various anticoagulants) is known to provide a stable measurement of NCEs [ 10 , 11 ]. Nevertheless, the effects of anticoagulants (except K2-EDTA) and acidic conditions on the analysis of 4β-HC in plasma have not been properly evaluated [ 12 , 13 , 14 , 15 ].…”

Database of 4 Million Medicinal Chemistry-Relevant Ring Systems

“…This required some fine-tuning to find a compromise between allowing sufficient novelty and diversity while keeping too exotic systems away. In addition to simple functionality counts, these rules also include a set of SMARTS patterns that should remove systems with low stability or high reactivity , for example, unstable acetals, esters, sulfones, sultones, diketones, and similar functionalities. The complete set of rules that have been applied is included in the Supporting Information.…”

Screening stabilisers for cyanoenone triterpenoid TX101 in rat plasma samples by simultaneous analysis of parent drug and the epoxidation product

“…The instability of drugs in biological matrices is often affected by pH, temperature, light, oxygen, enzymes and occasionally anticoagulants 3–5 . Controlling the pH, temperature, and avoiding exposure to light are relatively easy to achieve.…”