LC–ESI-MS/MS determination of in vivo metabolites of almotriptan in rat plasma, urine and feces: Application to pharmacokinetics
2012
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 20 mM 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 0.3 h of 5 mg/kg oral dose of almotriptan was determined to be 69.85 ng/mL.
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