By Roger Hayes, PhD
The adage “a little goes a long way” is an emerging reality in preclinical drug development, where new techniques in micro-volume sample analysis are yielding advantages for drug developers.
Traditionally, sample sizes of blood, plasma or serum needed for toxicokinetic (TK) and pharmacokinetic (PK) analysis often exceeded what’s allowed when using rodents, especially mice. The most common solution—taking samples from multiple rodents in satellite groups—isn’t ideal, as it means more animals used, greater inter-subject variability, and consequently increased development costs.
Fortunately, the volumes needed for bioanalysis have decreased in the past decade. We’re now in the era of microsampling, using significantly smaller volumes to measure drug concentrations or to detect biomarkers. Whereas some sample volumes once exceeded 200 mL, increasingly sensitive analytical techniques can drop the requirement to less than a tenth that amount in many cases.
How much less? Using the Gyros workstation, MPI Research investigators have obtained full PK profiles of a human IgG monoclonal antibody in a single mouse using just 10 mL of blood collected by tail vein at each time point following administration of the drug.
The benefits of such efficiency include savings in study cost (as much as 40—80 percent), decreased animal usage, less stress to the animal, quicker sampling, less use of the drug candidate under study, and a reduction of inter-subject variability for PK parameters.
Other advances that support microsampling include ultra-performance liquid chromatography, micro-solid phase extraction, and innovative source designs for mass spectrometers. For small molecule analytes, the sensitivity of routine quantitative assays has reached the picogram-per-microliter range.
Microsampling helps advance our commitment to the 3Rs—replace animal models where possible, reduce the number needed, and refine our processes to get the data required with minimal use of animals.
The effort to reduce sample volumes continues to evolve. In plasma sampling, a precise process of sample collection, centrifuging, and dilution allows bioanalysis of a 5 mL aliquot of sample, with a volume as little as 2 mL feasible. Over the past few years, the use of dried blood spot (DBS) samples—blood samples spotted on a collection card, air-dried, and stored and shipped at room temperature—has offered a much simpler and cost-effective alternative to a “wet” matrix, though it has some limitations related to hematocrit levels. An emerging alternative to DBS is a solid phase extraction device that can combine sampling, sample preparation, and extraction in one step.
MPI Research has embraced the precision, rigorous training, and expertise in the validated processes and technologies involved in microsampling. Doing so means we meet regulatory standards just as we meet the needs of our Sponsors: with high-quality results delivered quickly and cost-effectively. And that’s the most powerful advantage of all.
Roger Hayes, PhD, is Senior Vice President and General Manager of Laboratory Sciences at MPI Research. For more on cost-effective bioanalytical testing, contact firstname.lastname@example.org.