Dried blood spot analysis without dilution: Application to the LC-MS/MS determination of BMS-986001 in rat dried blood spot.
Sample dilution is one major challenge in dried blood spot (DBS) bioanalysis. To resolve this issue, we applied a no-dilution strategy for DBS analysis by using a calibration curve with very wide linear range. We developed an LC-MS/MS DBS assay with a linear range of 5 orders of magnitude (50-5000,000ng/mL) for BMS-986001, an HIV drug under development, by simultaneously monitoring two selective reaction monitoring transitions of different intensity. The assay was validated and successfully applied to the analysis of DBS samples collected in a toxicology study in rats dosed with BMS-986001. All samples were analyzed without any dilution. We also compared the concentration data generated from the DBS method and a validated plasma assay for the same study. The two sets of data agreed well with each other, demonstrating the validity of this strategy for DBS analysis. This approach provides an effective and convenient way to eliminate complicated dilution for DBS and other sample collection techniques.
Analytical and Bioanalytical Development, Bristol-Myers Squibb, Princeton, NJ 08543, USA. Electronic address: long.yuan@bms.com.
Long
L
Yuan
Analytical and Bioanalytical Development, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
Alan
A
Schuster
Analytical and Bioanalytical Development, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
Jim X
JX
Shen
Drug Safety Evaluation, Bristol-Myers Squibb, New Brunswick, NJ 08903, USA.
Pamela
P
Garrison-Borowski
Analytical and Bioanalytical Development, Bristol-Myers Squibb, Princeton, NJ 08543, USA.
Anne-Françoise
AF
Aubry
D000818:Animals; D019380:Anti-HIV Agents / Q000097:blood* / Q000633:toxicity; D002853:Chromatography, Liquid / Q000379:methods*; D005260:Female; D057230:Limit of Detection; D011247:Pregnancy; D051381:Rats; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000097:blood / Q000633:toxicity
D019380:Anti-HIV Agents; C583040:BMS-986001; D013936:Thymidine
Dilution; Dried blood spot; Extended linear range; LC–MS/MS; Quantitation; Regulated bioanalysis