Quantitation of the 5HT1D agonists MK-462 and sumatriptan in plasma by liquid chromatography-atmospheric pressure chemical ionization mass spectrometry.
The 5HT1D agonist sumatriptan is efficacious in the treatment of migraines. MK-462 is a drug of the same class which is under development in our laboratories. Bioanalytical methods of high efficiency, specificity and sensitivity were required to support the preclinical and clinical programs. These assays were based on HPLC with tandem MS-MS detection. MK-462 and sumatriptan were extracted using an automated solid-phase extraction technique on a C2 Varian Bond-Elut cartridge. The n-diethyl analogues of MK-462 and sumatriptan were used as internal standards. The analytes were chromatographed using reversed-phase (nitrile) columns coupled via a heated nebulizer interface to an atmospheric pressure chemical ionization source. The chromatographic run times were less than 7 min. Both methods were precise, accurate and selective down to plasma concentrations of 0.5 ng/ml. The assay for MK-462 was adapted to separately monitor the unlabeled and 14C-labeled species of the drug following intravenous administration of radiolabeled material to man.
McLoughlin
D A
DA
Merck Research Laboratories, West Point, PA 19486, USA.
Olah
T V
TV
Ellis
J D
JD
Gilbert
J D
JD
Halpin
R A
RA
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D011312:Pressure; D012016:Reference Values; D015203:Reproducibility of Results; D017366:Serotonin Receptor Agonists / Q000097:blood* / Q000494:pharmacology; D018170:Sumatriptan / Q000097:blood* / Q000494:pharmacology; D014230:Triazoles / Q000097:blood* / Q000494:pharmacology; D014363:Tryptamines
D017366:Serotonin Receptor Agonists; D014230:Triazoles; D014363:Tryptamines; C093622:rizatriptan; D018170:Sumatriptan