LC-ESI-MS/MS determination of in vivo metabolites of almotriptan in rat plasma, urine and feces: application to pharmacokinetics.

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. Copyright © 2012. Published by Elsevier B.V.

Citation

R Nageswara Rao, K Guruprasad, Ch Gangu Naidu, B Raju, R Srinivas. LC-ESI-MS/MS determination of in vivo metabolites of almotriptan in rat plasma, urine and feces: application to pharmacokinetics. Journal of chromatography. B, Analytical technologies in the biomedical and life sciences. 2012 Apr 1;891-892:44-51

Mesh Tags

Substances

PMID: 22406349

search → result