An evaluation of metabolite profiling of six drugs using dried blood spot

Abstract

1. Dry blood spot (DBS) analysis has been extensively used for the quantitative analysis of drugs by mass spectrometry; however, utilization of DBS for qualitative metabolite profiling has been very limited.

2. In the present study, we investigated the use of DBS for metabolite profiling of genistein, carbamazepine, losartan, sunitinib, sildenafil and zoniporide representing a range of Phase I and Phase II biotransformations following oral and intravenous dosing to rats. Plasma and DBS were collected for PK and metabolite profiling. Analyte extraction recovery from DBS was optimized using the parent compound and metabolite standard. Rat DBS metabolite profiles from all six compounds were similar to plasma metabolite profiles, however Phase II metabolites appeared to be extracted less efficiently from DBS compared to plasma, and compounds that were unstable in blood showed different metabolite profiles.

3. In summary, this study showed that in addition to PK bioanalytical analysis, DBS samples may also be utilized for metabolite profiling and a comparison of plasma and DBS metabolite profiling can also provide partitioning/association of major circulating metabolites compared to the parent drug even in the absence of a metabolite standard.

Keywords:

• Metabolite profiling
• biotransformation
• dry blood spot
• matrix comparison
• distribution
• phase I and II metabolism

Acknowledgements

Authors appreciate the method development and sample analysis from Sean Zhu and Scott Woodward at Q² Solutions. Appreciation also goes to Kenneth Cassidy for peer reviewing the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was supported by the Eli Lilly and Company.