title: LC-ESI-MS/MS determination of in vivo metabolites of almotriptan in rat plasma, urine and feces: application to pharmacokinetics.
abstract: A highly sensitive and specific liquid chromatography-electrospray ionization tandem mass spectrometric (LC-ESI-MS/MS) method for investigating the in vivo metabolites of almotriptan in rat plasma, feces and urine was developed. Chromatographic separation was achieved on a Lichrospher RP-18 column (250 mm × 4.6 mm, 5 μm), using 20mM ammonium acetate (pH 3.5) and acetonitrile (60:40, v/v) as a mobile phase at 25°C. MS/MS detection was performed by positive ion electrospray ionization using target ions at m/z 336 [M+H]⁺, m/z 368 and m/z 282 [M+H]⁺ for almotriptan and its two metabolites, respectively. Two metabolites viz., γ-aminobutyric acid and sulfonamide were detected in plasma as well as feces after 24 h of oral administration of almotriptan, while only γ-aminobutyric acid was found in urine. The method was sensitive with a lower limit of quantification of 1.43 ng/mL and linear over the range of 1.43-5000 ng/mL in plasma. The method was validated and successfully applied to a pharmacokinetic study of almotriptan in rat plasma using sumatriptan as an internal standard. The peak plasma concentration (C(max)) after 0.3h of 5mg/kg oral dose of almotriptan was determined to be 69.85 ng/mL.
authors.affiliation: Analytical Chemistry Division, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad 500607, India. rnrao@iict.res.in
authors.forename: R
authors.initials: R
authors.lastname: Nageswara Rao
authors.forename: K
authors.initials: K
authors.lastname: Guruprasad
authors.forename: Ch
authors.initials: Ch
authors.lastname: Gangu Naidu
authors.forename: B
authors.initials: B
authors.lastname: Raju
authors.forename: R
authors.initials: R
authors.lastname: Srinivas
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000493:pharmacokinetics*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014363:Tryptamines / Q000493:pharmacokinetics*
chemical_list: D017366:Serotonin Receptor Agonists; D014363:Tryptamines; C409045:almotriptan