Sensitive and specific liquid chromatographic–tandem mass spectrometric assay for dihydroergotamine and its major metabolite in human plasma

Pharmacologically Active Drug Metabolites: Impact on Drug Discovery and Pharmacotherapy

“…13). Its intrinsic potency is about thrice that of the parent (Hanoun et al, 2003), but more importantly, the plasma concentrations of the metabolite are 6-times greater (Wyss et al, 1991;Chen et al, 2002). It can be estimated that the metabolite possesses 20-fold greater in vivo activity than the parent, assuming that free fractions and brain penetrability properties are similar.…”

Simultaneous determination of microcystin-LR and its glutathione conjugate in fish tissues by liquid chromatography–tandem mass spectrometry

“…There have been many analytical methods for MC-LR, including protein phosphatase inhibition assay (PPIA) [15], enzyme-linked immunosorbent assay (ELISA) [16], liquid chromatography (LC) [17][18][19], capillary electrophoresis (CE) [20,21] and liquid chromatography-mass spectrometry (LC-MS) [22][23][24]. Because of its high specificity and sensitivity, liquid chromatography-tandem mass spectrometry (LC/MS/MS) has become the method of choice for quantitative determination of analytes in biological samples [25][26][27].…”

Identification and human pharmacokinetics of dihydroergotoxine metabolites in man: preliminary results

“…alpha-DHEP disposition [5], that dihydroergopeptide alkaloids undergo intense first-pass metabolism and that their pharmacokinetics in humans is characterized by large variability [6,7]. With regard to metabolism, data recently obtained with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) also show that oral dosing of dihydroergotamine [8] and DHEC [9] to young adults gives plasma levels of primary metabolites (OH-derivatives) several times greater than parent compounds, already in the first hour after dosing. In spite of this low metabolic stability, OH-metabolites of ergopeptide alkaloids are expected to behave as the pharmaceutically active ingredients with parent-like pharmacodynamics, as is the case for the 8 0 -OH-metabolites of dihydroergotamine [10][11][12][13] and bromocryptine (BCP) [14].…”