ISSUE NO. 16 — Microsampling in Drug Development

Microsampling significantly lessens the volume of blood and plasma/serum that is collected and analyzed to determine circulating concentrations of therapeutic drugs, metabolites, and biomarkers in preclinical and clinical research.

In preclinical research, microsampling technology supports the 3Rs of animal research, and allows for less intrusive blood collection procedures.

By definition, clinical microsampling reduces sample volume to less than or equal to 50 microlitres (μL) compared to conventional venipuncture wherein millilitres (mL) of blood volume is collected. In Altasciences’ experience, microsample volumes being analyzed are less than or equal to 20 μL, with some microsampling techniques as low as 5 μL.

In Issue 16 of The Altascientist, we explore the benefits, applications, and considerations of microsampling in preclinical, clinical, and bioanalytical research, including:

• Regulatory considerations
• Case study: Anti-Epileptic Drug Monitoring – Sample Preparation Using Impact-Assisted Extraction
• Case study: Large Molecule – Determination of Rituximab Using a Surrogate Peptide Approach

Benefits of Microsampling in Preclinical Research

Microsampling addresses two of the 3Rs (replacement and reduction) of preclinical research. By eliminating or greatly reducing the use of satellite animals, microsampling can reduce the number of rodents in certain preclinical studies by 30 to 40 percent. Decreasing the number of animals required can have an added benefit of reducing R&D costs related to animals and housing, particularly for toxicokinetic (TK) studies that use satellite animals to minimize repeated conventional blood sampling procedures.

Lower-volume blood draws, from both rodents and non-rodents, taken from less disruptive locations, allow lab animals to recover more quickly, and have fewer sampling-related adverse events compared to conventional sampling. Refinement of the bleeding technique also translates to less animal handling, minimizing stress.

The elimination of satellite animals improves the quality of research data, as scientists conduct all TK analysis using main study animals. This enables direct correlation of exposure with pharmacodynamic and toxicological outcomes.

Benefits of Microsampling in Clinical Research

Microsampling in clinical research reduces patient burden, improves enrollment and engagement, and reduces drop-out. Self-administration facilitates the data collection during studies related to unpredictable clinical episodes, such as acute migraine or epilepsy attacks, and allows episodic sampling to relate efficacy with bioavailability. The dried blood samples can be stored and transported at ambient temperature, eliminating the costly cryopreservation and shipment that conventional wet blood samples demand.

Microsampling also provides a convenient, low-cost way to collect blood and plasma/serum from patients remotely. Individuals in remote geographic locations are able to participate in clinical trials, as they can conduct their blood draws at home.

Bioanalytical Considerations for Microsampling

The accurate analysis of dried blood microsamples requires equipment with high sensitivity and specificity, such as that offered by triple-stage quadrupole mass spectrometry systems paired with liquid chromatography front ends to optimize signal-to-noise ratio. When additional selectivity is required, this can be addressed by accurate mass filtering (e.g., time-of-flight or orbitrap mass spectrometer) or the use of differential ion mobility spectrometry to separate analyte from interference prior to mass selection.

Is Microsampling the Right Option for Your Preclinical or Clinical Study?

Microsampling is not appropriate for all studies and should be considered on a case-by-case basis. In a microsampling drug development program, it is critical to establish the appropriate pharmacokinetic/ statistical considerations to enable correlation/concordance between microsampling and standard blood sampling techniques.

How Altasciences Can Help

Altasciences’ scientific acumen and experience with different microsampling devices, supporting numerous programs, has led to unparalleled expertise in the development of assays and processes for all your drug candidates, from the straightforward to the most complex.

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