Microsampling of Liquid Plasma and Dry Milk in Pre-Clinical and Clinical Studies

The adoption of microsampling approaches in non-clinical laboratory studies offers significant benefits in terms of animal welfare and reduction of invasive procedures for toxicokinetic (TK) sample collection. Microsampling not only provides a full TK profile from each animal, but the technique can also enable Day 1 TK sample collection in rodent studies. Typically, study Day 1 TK samples are not collected in rodent studies when large volume sparse sampling technique is used. After in vitro and in vivo evaluation of different small volume blood collection devices, the 100 uL Sarstedt Minivette® was selected as the preferred microsampling blood collection device. The 100 uL blood volume per sample provides sufficient plasma volume for using automation and dilution of samples for regulated bioanalysis. When needed, an esterase inhibitor or other additives can be used during the sample collection process when certain stability issues are encountered for an analyte.

Volumetric absorptive microsampling (VAMS) is a microsampling technique that involves the collection of a precise volume of blood or other biological fluids onto a polymeric absorbent tip. In this presentation, the focus is on demonstrating the application of VAMS technique for the collection and determination of Suvorexant and its metabolite in human milk. Human breast milk is an exceedingly complicated matrix. The high fat content can create issues by differentially partitioning drugs and metabolites between milk’s aqueous and lipid phases. Freezing of liquid milk can also potentially lead to phase separation and difficulty in reliably measuring concentration of drugs and metabolites. We successfully developed a VAMS milk collection method and validated a bioanalytical assay to quantify Suvorexant and its metabolite in human milk. The approach described in this presentation was successfully applied to provide bioanalytical support for a post-approval lactation clinical study.