Using Mitra sampling to support first-in-human pharmacokinetic evaluations for PF-07059013

Area of Science:

• Pharmacokinetics and Drug Metabolism
• Analytical Chemistry
• Biomedical Science

Background:

• Accurate quantification of drug concentrations in biological matrices is crucial for pharmacokinetic studies.
• Dried blood spot (DBS) sampling offers advantages over traditional venipuncture, including ease of collection and reduced sample volume.
• Developing and validating robust analytical methods for DBS is essential for their widespread clinical adoption.

Purpose of the Study:

• To develop and validate a sensitive and selective analytical method for determining PF-07059013 concentrations in human dried blood spots.
• To evaluate the impact of critical parameters like hematocrit and Mitra™ tip lot variation on assay accuracy.
• To assess the method's performance in a clinical setting and compare it with liquid blood sample analysis.

Main Methods:

• Dried blood samples collected on Mitra™ tips were used.
• PF-07059013 was extracted from 10 μL of dried blood using methanol.
• High-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) was employed for analysis.

Main Results:

• A validated method for PF-07059013 determination in dried blood was established with a quantification range of 50 to 50,000 ng/mL.
• The assay demonstrated robustness against variations in hematocrit and Mitra™ tip lot.
• The method exhibited excellent performance in a clinical study, with a correlation coefficient of 0.95 between dried and liquid blood samples.

Conclusions:

• The developed HPLC-MS/MS method is suitable for the accurate quantification of PF-07059013 in human dried blood spots.
• The method's reliability is confirmed by its performance in a clinical study and its strong correlation with liquid blood measurements.
• This validated assay supports the use of dried blood sampling for PF-07059013 pharmacokinetic monitoring in clinical trials.