A high-performance liquid chromatographic method for determination of the niguldipine analogue DHP-014

Zhou, Xiaofei; Wang, Qi; Coburn, Robert A.; Morris, Marilyn E.

doi:10.1002/bmc.526

Cited by 2 publications

(2 citation statements)

References 13 publications

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“…Their functions are attributed to the inhibition of cellular influx of calcium, resulting in vasodilatation and reduction of blood pressure []. Various approaches have been reported for the separation of 1,4‐DHPs, including HPLC‐UV [], MEKC [], molecularly imprinted polymer (MIP)‐CEC [], and high performance thin layer chromatography (HPTLC) []. Despite these achievements, OT‐CEC has never been applied for analysis of 1,4‐DHPs and it is a competitive method in terms of simplicity, reusability, and high speed.…”

Section: Introductionmentioning

confidence: 99%

A well‐defined block copolymer serving as surfactants in separation of 1,4‐dihydropyridines by open‐tubular capillary eletrochromatography

Qiao

et al. 2012

Electrophoresis

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A novel series of diblock copolymers, poly(butyl methacrylate)(n) -block-poly(glycidyl methacrylate)(m) [P(BMA)(n) -b-P(GMA)(m) ], were synthesized by atom transfer radical polymerization and developed as covalent coating of capillaries. The excellent performance of this coating in separation of three 1,4-dihydropyridines (DHPs) derivatives (amlodipine, nicardipine, nitrendipine) was achieved when the diblock copolymers self-assembled into micelles, which was confirmed by transmission electron microscopy, dynamic light scattering, and atom force microscopy. Meanwhile, the effects of block ratio n/m, pH value, buffer concentration, and organic solvents on the separation of 1,4-DHPs were investigated in detail. Then, the relationship between the morphologies of copolymers and the separation resolutions of 1,4-DHPs was discussed. Furthermore, the proposed method exhibited good run-to-run and column-to-column precision with relative standard deviations of electroosmotic flow less than 3.0%. It was also validated with linearity of three 1,4-DHPs in the range of 0.01-1.80 mM (r(2) ≥ 99.7%), efficient recovery (94-103%), and good repeatability (≤ 3.8%). In addition, three 1,4-DHPs were successfully separated in the spiked human serum sample, which indicated the potential utility of this method in biological sample analysis.

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Section: Introductionmentioning

confidence: 99%

A well‐defined block copolymer serving as surfactants in separation of 1,4‐dihydropyridines by open‐tubular capillary eletrochromatography

Qiao

et al. 2012

Electrophoresis

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“…A validated HPLC method [6] was used to determine ( AE )-DHP-014 in rat plasma. Briefly, ( AE )-DHP-014 and niguldipine hydrochloride (the internal standard) were extracted from rat plasma by rapid liquid extraction using hexane.…”

Section: Determination Of ( Ae )-Dhp-014 In Rat Plasmamentioning

confidence: 99%

Pharmacokinetics and bioavailability of a newly synthesized dihydropyridine compound with multidrug resistance reversal activity

Zhou¹,

MacDiarmid²,

Coburn³

et al. 2005

Biopharm. Drug Dispos.

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(+/-)3-(3-(4,4-diphenylpiperidin-1-yl)propyl) 5-methyl 4-(3,4-dimethoxyphenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate ((+/-)-DHP-014), is a new 4-aryl-1,4-dihydropyridine that can reverse multidrug resistance mediated by the ATP-binding cassette (ABC) transport proteins, P-glycoprotein, multidrug resistance-associated protein 1 and breast cancer resistance protein; it exhibits negligible calcium channel blocking activity. The objective of this work was to investigate the pharmacokinetics of this new compound in rats. Three intravenous (1, 2 and 5 mg/kg) and two oral (25 and 50 mg/kg) doses were administered to female Sprague-Dawley rats. A two-compartment model with nonlinear elimination best characterized the pharmacokinetic profiles after intravenous and oral administration in rats. The terminal half-life of (+/-)-DHP-014 increased and the systemic clearance significantly decreased at higher doses, indicating nonlinear elimination. The dose-dependent clearance is likely due to saturation of metabolism. The apparent volume of distribution of (+/-)-DHP-014 was 2.0 L/kg in rats and was unchanged with increasing intravenous doses of (+/-)-DHP-014. The estimated oral bioavailability of (+/-)-DHP-014 was 8.2%. The poor bioavailability is likely due to the poor solubility of the compound, as well as to substantial first-pass elimination.

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A high-performance liquid chromatographic method for determination of the niguldipine analogue DHP-014

Cited by 2 publications

References 13 publications

A well‐defined block copolymer serving as surfactants in separation of 1,4‐dihydropyridines by open‐tubular capillary eletrochromatography

A well‐defined block copolymer serving as surfactants in separation of 1,4‐dihydropyridines by open‐tubular capillary eletrochromatography

Pharmacokinetics and bioavailability of a newly synthesized dihydropyridine compound with multidrug resistance reversal activity

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