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Sensitive triple‐quadrupole mass spectrometric assay for the determination of BMS‐181885, a 5‐HT1 agonist, in human plasma following solid phase extraction
Author(s) -
Chang ShuYing,
Whigan Daisy,
Shyu Wen Chyi,
Srinivas Nuggehally R.
Publication year - 1999
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/(sici)1099-0801(199910)13:6<425::aid-bmc905>3.0.co;2-g
Subject(s) - chemistry , chromatography , ammonium formate , selected reaction monitoring , triple quadrupole mass spectrometer , mass spectrometry , detection limit , extraction (chemistry) , solid phase extraction , acetonitrile , standard curve , analytical chemistry (journal) , ammonium acetate , solvent , quadrupole mass analyzer , high performance liquid chromatography , tandem mass spectrometry , organic chemistry
A sensitive, selective, accurate, precise and reproducible triple‐quadrupole liquid chromatographic–mass spectrometric assay was developed and validated for BMS‐181885 (I), a 5HT1 agonist, in human plasma using BMS‐181101 as the internal standard (IS). The method involved solid phase extraction of plasma containing I and the IS using Isoelute CN cartridges. The supernatant was then evaporated to dryness at 40°C. The residue was dissolved in 100 µL of the injecting solvent. The HPLC ccolumn was ODS‐3, 2 × 100 mm. The mobile phase comprised 10 m M ammonium formate (pH = 4) and acetonitrile, 55:45 v/v, used in an isocratic condition. The mass spectrometer was programmed to admit the protonated molecules at m / z 461 (I) and m / z 370 (IS) via the first quadrupole filter and to select reaction monitoring of ions at m / z 152 for I and IS for the quantification. Standard curves were fitted to a weighted quadratic function over the concentration range 0.2–200 ng/mL. The lowest standard concentration (0.2 ng/mL) was experimentally established as the lower limit of quantitation of the assay. The mean predicted quality control concentrations deviated within ± 11% of the corresponding nominal values; the intra‐assay and inter‐assay precisions were within 7.0% relative standard deviation. I was stable in the injection solvent at 4°C for at least 24 h and for at least three freeze–thaw cycles. Freezer stability of I in plasma was demonstrated for at least 3 months. The extraction recovery of I was established as 97%. The validated assay was applied to a pharmacokinetic study of I in humans. Copyright © 1999 John Wiley & Sons, Ltd.