Bioanalysis of dried saliva spot (DSS) samples using detergent-assisted sample extraction with UHPLC-MS/MS detection
Naiyu Zheng1, Jianing Zeng1, Qin C Ji1
1Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
Analytica Chimica Acta
|August 11, 2016
Summary
Dried saliva spot (DSS) sampling enables convenient home collection for migraine drug pharmacokinetic studies. This non-invasive method, using detergent-assisted extraction, successfully quantified BMS-927711 in human saliva, proving its clinical utility.
Area of Science:
- Bioanalysis
- Pharmacokinetics
- Analytical Chemistry
Background:
- Dried saliva spot (DSS) sampling offers a non-invasive, patient-friendly alternative for bioanalysis, suitable for home-based sample collection.
- Accurate quantification of drug candidates in biological matrices is crucial for pharmacokinetic evaluations, especially for conditions like migraines.
- Traditional blood sampling methods can be invasive and require clinical visits, posing challenges for real-time pharmacokinetic monitoring during acute events.
Purpose of the Study:
- To develop and validate a novel ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) assay for quantifying BMS-927711 in human DSS.
- To assess the feasibility of home-based DSS sampling for pharmacokinetic studies of BMS-927711 in migraine patients.
- To investigate the efficacy of detergent-assisted extraction for improving analyte recovery in DSS samples.
Main Methods:
- Developed a UHPLC-MS/MS assay using Whatman FTA™ DMPK-C cards for DSS collection and 4-mm punch extraction.
- Employed detergent-assisted sonication with Triton-X-100 and liquid-liquid extraction for sample preparation.
- Utilized an Aquity® UPLC BEH C18 Column and a Triple Quad™ 5500 mass spectrometer for analysis.
Main Results:
- The UHPLC-MS/MS assay demonstrated linearity over a concentration range of 2.00 to 1000 ng/mL for BMS-927711 in human saliva.
- Achieved excellent assay performance with intra- and inter-assay precision within 8.8% CV and accuracy within ±6.7% Dev.
- Successfully detected and quantified BMS-927711 in human DSS, confirming the method's applicability in a clinical pharmacokinetic study.
Conclusions:
- The developed UHPLC-MS/MS assay coupled with DSS sampling is suitable for determining BMS-927711 pharmacokinetics in migraine patients, enabling convenient home collection.
- Detergent-assisted extraction, specifically using Triton-X-100, proved effective in enhancing analyte recovery, offering a valuable technique for DSS and other dried matrix spot assays.
- This study validates DSS as a practical and reliable bioanalytical sample collection method for at-home use in clinical trials.
Keywords:
BMS-927711Detergent-assisted sample extractionDried saliva spot (DSS)Pharmacokinetic studyQuantitationUltra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)
