DBS direct elution: optimizing performance in high-throughput quantitative LC-MS/MS analysis.
BACKGROUND
Automated DBS direct elution techniques eliminate the manual extraction burden of DBS bioanalysis, offer good quantitative performance, the ability to eliminate hematocrit-based assay bias, and, previous reports have demonstrated that significant increases in assay sensitivity compared with manual DBS extraction are possible.


RESULTS
An investigation into elucidating parameters for optimized generic DBS direct elution for high sample throughput quantitative bioanalytical applications is presented for the first time. Generic direct elution conditions were identified that enabled LC-MS/MS assay sensitivity to be maximized while retaining acceptable chromatographic performance.


CONCLUSIONS
Compared with generic conventional DBS manual extraction, assay sensitivity was demonstrated to be increased up to 33-fold across four representative small molecule compounds, using the recommended direct elution conditions.
Bioanalytical Science & Toxicokinetics, Drug Metabolism & Pharmacokinetics, Platform Technologies & Sciences, GlaxoSmithKline, R&D, Ware, SG12 0DP, UK.|Faculty of Engineering & Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent, ME4 4TB, UK.
Paul
P
Abu-Rabie
Bioanalytical Science & Toxicokinetics, Drug Metabolism & Pharmacokinetics, Platform Technologies & Sciences, GlaxoSmithKline, R&D, Ware, SG12 0DP, UK.
Neil
N
Spooner
Faculty of Engineering & Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent, ME4 4TB, UK.
Babur Z
BZ
Chowdhry
Faculty of Engineering & Science, University of Greenwich, Medway Campus, Chatham Maritime, Kent, ME4 4TB, UK.
Frank S
FS
Pullen
D002853:Chromatography, Liquid / Q000379:methods*; D059788:Dried Blood Spot Testing / Q000379:methods*; D057166:High-Throughput Screening Assays / Q000379:methods; D006801:Humans; D059625:Liquid-Liquid Extraction / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013997:Time Factors