| Author |
Zheng, Naiyu Zeng, Jianing Ji, Qin C. Angeles, Aida Aubry, Anne-Francoise Basdeo, Shenita Buzescu, Adela Landry, Ishani Savant Jariwala, Navin Turley, Wesley Burrell, Richard Arnold, Mark E. |
| Description |
Author Affiliation: Zheng N ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. Electronic address: naiyu.zheng@bms.com.); Zeng J ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. Electronic address: jianing.zeng@bms.com.); Ji QC ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Angeles A ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Aubry AF ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Basdeo S ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Buzescu A ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Landry IS ( Early Clinical & Translational Research, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Jariwala N ( Early Clinical & Translational Research, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.); Turley W ( Discovery Chemistry, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA.); Burrell R ( Discovery Chemistry, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA.); Arnold ME ( Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.) |
| Abstract |
Dried saliva spot (DSS) sampling is a non-invasive sample collection technique for bioanalysis that can be potentially implemented at the patient's home. A UHPLC-MS/MS assay was developed using detergent-assisted sample extraction to quantify BMS-927711, a drug candidate in development for the treatment of migraines, in human DSS. By implementing DSS sampling at the patients' home, the bioanalytical sample collection for pharmacokinetic evaluation can be done at the time of the acute migraine attack without the need for clinical visits. DSS samples were prepared by spotting 15 µL of liquid saliva onto regular Whatman FTA™ DMPK-C cards and verified with a UV lamp (at λ 254 nm or 365 nm) during DSS punching. The 4-mm DSS punches in a 96-well plate were sonicated with 200 µL of [(13)C2, D4]-BMS-927711 internal standard (IS) solution in 20/80 MeOH/water for 10 min, followed by sonication with 50 µL of 100 mM NH4OAc with 1.0% Triton-X-100 (as detergent) prior to liquid-liquid extraction with 600 µL EtOAc/Hexane (90:10). UHPLC-MS/MS was performed with an Aquity(®) UPLC BEH C18 Column (2.1 × 50 mm, 1.7 µm) on a Triple Quad™ 5500 mass spectrometer. The assay was linear with a concentration range from 2.00 to 1000 ng mL(-1) for BMS-927711 in human saliva. The intra- and inter-assay precision was within 8.8% CV, and the accuracy was within ±6.7% Dev of the nominal concentration values. This UHPLC-MS/MS assay has been successfully applied to determine the drug's pharmacokinetics within a clinical study. For the first time, we observed BMS-927711 exposure in human DSS, confirming the suitability of this sampling technique for migraine patients to use at home. Detergent-assisted extraction with Triton-X-100 could be very useful in DSS or other dried matrix spot (DMS) assays to overcome low or inconsistent analyte recovery issues. |
