Synthesis and 5‐HT2A, 5‐HT1A and α1‐Binding Affinities of 2‐[2‐Hydroxy‐3‐(pyridin‐3‐yl‐methyl)amino]‐, 2‐[2‐Hydroxy‐3‐(2‐pyridin‐2‐yl‐ethyl)amino]‐ and 2‐[2‐Hydroxy‐3‐(4‐N‐methyl‐piperazin‐1‐yl)‐amino]propoxybenzaldehyde‐O‐(substituted) Benzyl Oximes

Orlandini, Elisabetta; Rapposelli, Simona; Nencetti, Susanna; Giannaccini, Gino; Betti, Laura; Balsamo, Aldo

doi:10.1002/ardp.200600123

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Sarpogrelate was developed as a 5-hydroxytryptamine (5-HT) 2A-receptor antagonist [ 1 , 2 ] and is used for the treatment of peripheral arterial disease. Its metabolite, M-1, produced by hydrolysis, is also a potent 5-HT2A-receptor antagonist [ 3 , 4 ]. While sarpogrelate has antiplatelet, antithrombotic, antimitogenic, and antiatherosclerotic properties [ 5 ], its therapeutic concentration range remains unclear.…”

Section: Introductionmentioning

confidence: 99%

A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application

et al. 2015

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BackgroundThis study describes a novel analytical method for simultaneously determining sarpogrelate and its metabolite (M-1) in human plasma, using liquid chromatography coupled with tandem mass spectrometry, with electrospray ionization in the positive ion mode.MethodsSarpogrelate, M-1, and labeled internal standard (d3-sarpogrelate) were extracted from 50 µL of human plasma by simple protein precipitation. Chromatographic separation was performed by using a linear gradient elution of a mobile phase involving water-formic acid (99.9:0.1, v/v) and acetonitrile-formic acid (99.9:0.1, v/v) over 4 min of run time on a column, with a core-shell-type stationary phase (Kinetex C18, 50 mm×2.1 mm i.d., 2.6-µm particle size, Phenomenex, USA). Detection of the column effluent was performed by using a triple-quadruple mass spectrometer in the multiple-reaction monitoring mode.ResultsThe developed method was validated in human plasma, with lower limits of quantification of 10 ng/mL for sarpogrelate and 2 ng/mL for M-1. The calibration curves of sarpogrelate and M-1 were linear over the concentration ranges of 10-2,000 and 2-400 ng/mL, respectively (R2>0.99). The carry-over effect, precision, accuracy, and stability of the method met the criteria for acceptance.ConclusionsA simple, fast, robust, and reliable analytical method was successfully developed and applied to the high-throughput determination of sarpogrelate and its metabolite in real plasma samples in a pharmacokinetic study of healthy subjects.

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Section: Introductionmentioning

confidence: 99%

A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application

et al. 2015

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“…A potent competitive antagonist of this receptor is sarpogrelate. In addition, a metabolite of sarpogrelate (M‐1), produced by ester hydrolysis, is also a potent antagonist of the 5‐HT 2A receptor . Sarpogrelate inhibits platelet aggregation and vasoconstriction and has been widely applied to treat peripheral vascular disease in Asia .…”

mentioning

confidence: 99%

Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4‐Way Replicate Crossover Investigation by a Reference‐Scaled Average Bioequivalence Approach

Ding

Liu

Lou

et al. 2018

Clinical Pharm in Drug Dev

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Sarpogrelate is widely used to treat peripheral vascular disorders. However, it has been demonstrated to have a poor pharmacokinetic (PK) profile and marked within‐subject variability. Here, the bioequivalence of 2 formulations of sarpogrelate (100‐mg tablets) was assessed by using the reference‐scaled average bioequivalence (RSABE) method, and the PK parameters were quantified in healthy Chinese subjects under fasting (n = 38) and fed (n = 35) conditions. In this open and randomized 4‐way replicate study, a single dose of sarpogrelate was administered followed by a 3‐day washout period. The sarpogrelate concentration in blood samples was measured by liquid chromatography‐tandem mass spectrometry within 6 hours (fasting) or 10 hours (fed) of drug administration, and the PK parameters were determined by a noncompartmental model. The bioequivalence of the 2 formulations under both conditions was assessed using the ratios of ln(peak concentration [Cmax]) and ln(area under the concentration‐time curve [AUC]) within the limits based on the RSABE method. The 90% CIs for the ratios of lnCmax, lnAUC0‐t, and lnAUC0‐∞ were 0.8531–1.1100, 0.9616–1.0737, and 0.9550–1.0684, respectively, under fasting conditions and 0.8918–1.1076, 0.9818–1.0694, and 0.9818–1.0686, respectively, under fed conditions, which were within the RSABE acceptance limits. Food intake decreased the systemic exposure and the Cmax of sarpogrelate by 0.9‐fold and 0.5‐fold, respectively.

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Cited by 2 publications

References 17 publications

A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application

A Novel Simultaneous Determination of Sarpogrelate and its Active Metabolite (M-1) in Human Plasma, Using Liquid Chromatography-Tandem Mass Spectrometry: Clinical Application

Bioequivalence of Sarpogrelate in Healthy Chinese Subjects Under Fasting and Fed Conditions: A 4‐Way Replicate Crossover Investigation by a Reference‐Scaled Average Bioequivalence Approach

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