title: Development and validation of a sensitive and rapid method to determine naratriptan in human plasma by LC-ESI-MS-MS: application to a bioequivalence study.
abstract: A simple, sensitive, selective, and rapid high-performance liquid chromatography-tandem mass spectrometry method is developed and validated for the quantitation of naratriptan, using sumatriptan as internal standard (IS). The method included liquid-liquid extraction of naratriptan and IS with methyl-tert-butyl ether and dichloromethane mixture from 100 μL human plasma. The chromatographic separation is achieved on ACE C18 (50 mm × 2.1 mm, 5 μm) analytical column under isocratic conditions, using 0.1% acetic acid and acetonitrile (15:85, v/v) at a flow-rate of 0.4 mL/min. The precursor → product ion transitions for naratriptan (m/z 336.10 → 98.06) and IS (m/z 296.09 → 251.06) were monitored on a triple quadrupole mass spectrometer, operating in the multiple reaction monitoring (MRM) and positive ion mode. The linearity of the method for naratriptan is determined in the range of 103-20690 pg/mL with the analysis time of 1.5 min. The method is fully validated according to USFDA guidelines. A systematic post-column infusion study is conducted for ion-suppression due to endogenous matrix components. The process efficiency of analyte (96%) and IS (93%) from spiked plasma samples was consistent and reproducible. The application of the method is demonstrated by a bioequivalence study of 2.5 mg naratriptan tablet formulation in 31 healthy volunteers under fasting conditions.
authors.affiliation: Bioanalytical Research Department, Veeda Clinical Research, Ahmedabad 3800015, India.
authors.forename: Manish
authors.initials: M
authors.lastname: Yadav
authors.forename: Chirag
authors.initials: C
authors.lastname: Patel
authors.forename: Mahendra
authors.initials: M
authors.lastname: Patel
authors.forename: Tulsidas
authors.initials: T
authors.lastname: Mishra
authors.forename: Girin A
authors.initials: GA
authors.lastname: Baxi
authors.forename: Puran
authors.initials: P
authors.lastname: Singhal
authors.forename: Pranav S
authors.initials: PS
authors.lastname: Shrivastav
mesh_terms: D000328:Adult; D019540:Area Under Curve; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D010880:Piperidines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D018170:Sumatriptan / Q000032:analysis / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D013810:Therapeutic Equivalency; D014363:Tryptamines / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics*
chemical_list: D010880:Piperidines; D014363:Tryptamines; D018170:Sumatriptan; C106783:naratriptan