title: Bioanalysis of dried saliva spot (DSS) samples using detergent-assisted sample extraction with UHPLC-MS/MS detection.
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.
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. Electronic address: naiyu.zheng@bms.com.
authors: Naiyu
authors: N
authors: Zheng
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA. Electronic address: jianing.zeng@bms.com.
authors: Jianing
authors: J
authors: Zeng
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Qin C
authors: QC
authors: Ji
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Aida
authors: A
authors: Angeles
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Anne-Francoise
authors: AF
authors: Aubry
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Shenita
authors: S
authors: Basdeo
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Adela
authors: A
authors: Buzescu
authors: Early Clinical & Translational Research, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Ishani Savant
authors: IS
authors: Landry
authors: Early Clinical & Translational Research, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Navin
authors: N
authors: Jariwala
authors: Discovery Chemistry, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA.
authors: Wesley
authors: W
authors: Turley
authors: Discovery Chemistry, Bristol-Myers Squibb Company, Wallingford, CT 06492, USA.
authors: Richard
authors: R
authors: Burrell
authors: Analytical & Bioanalytical Operation, Bristol-Myers Squibb Company, Princeton, NJ 08543, USA.
authors: Mark E
authors: ME
authors: Arnold
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003902:Detergents / Q000737:chemistry*; D006801:Humans; D059625:Liquid-Liquid Extraction; D010880:Piperidines / Q000032:analysis*; D011725:Pyridines / Q000032:analysis*; D012463:Saliva / Q000737:chemistry*; D053719:Tandem Mass Spectrometry
chemical_list: D003902:Detergents; D010880:Piperidines; D011725:Pyridines; C578443:rimegepant sulfate
keywords: BMS-927711; Detergent-assisted sample extraction; Dried saliva spot (DSS); Pharmacokinetic study; Quantitation; Ultra-high performance liquid chromatography–tandem mass spectrometry (UHPLC-MS/MS)