Assay of nicergoline and three metabolites in human plasma and urine by high-performance liquid chromatography—atmospheric pressure ionization mass spectrometry

Banno, Kiyoshi; Horimoto, Shingo; Mabuchi, Masanari

doi:10.1016/0378-4347(91)80175-c

Cited by 16 publications

(6 citation statements)

References 15 publications

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“…A qualitative RP-HPLC-UV study was reported for NIC and some related compounds including 1-DN and 5-CN, but no quantitation was reported in this study [2]. 5-CN was used as an internal standard, but it was not quantified by the RP-HPLC (API-MS) method [7]. NIC and some metabolites were determined by a TLC-SIMS method [8].…”

Section: Introductionmentioning

confidence: 97%

An efficient separation and method development for the quantifying of two basic impurities of Nicergoline by reversed-phase high performance liquid chromatography using ion-pairing counter ions

Yalçın

Yüktaş

2006

Journal of Pharmaceutical and Biomedical Analysis

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Section: Introductionmentioning

confidence: 97%

An efficient separation and method development for the quantifying of two basic impurities of Nicergoline by reversed-phase high performance liquid chromatography using ion-pairing counter ions

Yalçın

Yüktaş

2006

Journal of Pharmaceutical and Biomedical Analysis

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“…Consequently, almost no nicergoline could be detected in human plasma and pharmacokinetic studies of nicergoline have been mainly based on the determination of MDL. To our knowledge, some methods, such as radioimmunoassay [5] , [6] , HPLC–UV [7] , [8] and HPLC–MS [9] , [10] , [11] , have been used for the determination of nicergoline and its metabolite MDL in biological matrixes.…”

Section: Introductionmentioning

confidence: 99%

Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies

Zheng

Dexi

et al. 2012

Journal of Pharmaceutical Analysis

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A fast, simple and sensitive high performance liquid chromatographic (HPLC) method has been developed for determination of 10α-methoxy-6-methyl ergoline-8β-methanol (MDL, a main metabolite of nicergoline) in human plasma. One-step liquid–liquid extraction (LLE) with diethyl ether was employed as the sample preparation method. Tizanidine hydrochloride was selected as the internal standard (IS). Analysis was carried out on a Diamonsil ODS column (150 mm×4.6 mm, 5 μm) using acetonitrile–ammonium acetate (0.1 mol/L) (15/85, v/v) as mobile phase at detection wavelength of 224 nm. The calibration curves were linear over the range of 2.288–73.2 ng/mL with a lower limit of quantitation (LLOQ) of 2.288 ng/mL. The intra- and inter-day precision values were below 13% and the recoveries were from 74.47% to 83.20% at three quality control levels. The method herein described was successfully applied in a randomized crossover bioequivalence study of two different nicergoline preparations after administration of 30 mg in 20 healthy volunteers.

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“…Interestingly, N‐ hydroxymethyl derivatives have been reported as prodrug candidates, the active compound being the demethylated metabolite [7]. However, carbinol‐amines or carbinol‐amides P450 metabolites have been reported in the case of benzylic tertiary amine (clebopride 1 [8]), aromatic amines ( N‐ methylcarbazole 2 [9–14] or nicergoline 3 [15–19]), dialkylated‐aliphatic amides [20–22], cotinine 4 [23], dialkylated‐aromatic amides (benzamide derivatives [24,25] or triazolyl‐benzophenone derivatives 5 [26]), N‐ methyl‐imide ( N‐ methylphthalimide 6 [7]) or N ‐substituted urea derivatives (ritonavir 7 [27]). The chemical structures of these molecules are given in Scheme 1.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of N‐methyl‐amide by cytochrome P450s

Perrin¹,

Loiseau²,

André³

et al. 2011

The FEBS Journal

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We report unambiguous proof of the stability of a carbinol intermediate in the case of P450 metabolism of an N‐methylated natural cyclo‐peptide, namely tentoxin. Under mild acidic or neutral conditions, the lifetime of carbinol‐amide is long enough to be fully characterized. This metabolite has been characterized using specifically labeled 14C‐methyl tentoxin isotopomers, HPLC, HPLC‐MS, MS‐MS and NMR. Under stronger acidic conditions, the stability of this metabolite vanishes through deformylation. A theoretical mechanistic investigation reveals that the stability is governed by the accessibility of the nitrogen lone pair and its protonation state. For carbinol‐amines, even in neutral conditions, the energy barrier for deformylation is low enough to allow rapid deformylation. Carbinol‐amide behaves differently. Under neutral conditions, delocalization of the nitrogen lone pair increases the energy barrier of deformylation that is a slow process under such conditions. After protonation, we were able to optimize a deformylation transition that is lower in energy and thus accounts for the lower stability of carbinol‐amides observed experimentally in acidic conditions. Finally, by considering the protocol usually used for extraction and analysis of this type of metabolite, carbinol‐amide may thus be frequently ignored in drug metabolism pathways.

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Assay of nicergoline and three metabolites in human plasma and urine by high-performance liquid chromatography—atmospheric pressure ionization mass spectrometry

Cited by 16 publications

References 15 publications

An efficient separation and method development for the quantifying of two basic impurities of Nicergoline by reversed-phase high performance liquid chromatography using ion-pairing counter ions

An efficient separation and method development for the quantifying of two basic impurities of Nicergoline by reversed-phase high performance liquid chromatography using ion-pairing counter ions

Determination of metabolite of nicergoline in human plasma by high-performance liquid chromatography and its application in pharmacokinetic studies

Metabolism of N‐methyl‐amide by cytochrome P450s

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