Simultaneous analysis of the enantiomers of verapamil and norverapamil in rat plasma by liquid chromatography-tandem mass spectrometry

Mateus, Fabiano Henrique; Lepera, José Salvador; Marques, Maria Paula; Boralli, Vanessa Bergamin; Lanchote, Vera Lúcia

doi:10.1016/j.jpba.2007.09.021

Cited by 12 publications

(18 citation statements)

References 15 publications

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“…In contrast, a similar concentration of R-(+)-VER results in vasodilatation of the arterial and coronary vasculature, but is relatively devoid of direct cardiac effects (Mateus et al, 2007;Pagel et al, 1998). S-(-)-VER is 10-20 times more potent than R-(+)-VER in slowing the cardiac A-V conduction velocity in humans, dogs and rabbits (Lankford and Bai, 1995;Mateus et al, 2007). Although R-(+)-VER has been shown to have lower antiarrhythmic potency, studies have found that this enantiomer has anti-tumor activity (Uehara et al, 1993;Warmann et al, 2002).…”

Section: Ver Is a Chiral Drug That Is Administered As A Racemic Mixtumentioning

confidence: 96%

“…These enantiomers have different pharmacodynamic and pharmacokinetic properties (Lankford and Bai, 1995;Mateus et al, 2007;Pagel et al, 1998;Bhatti and Foster, 1997;Robinson and Mehvar, 1996). S-(-)-VER has negative chronotropic and inotropic effects, delays atrioventricular node conduction and causes systemic and coronary artery vasodilatation.…”

Section: Ver Is a Chiral Drug That Is Administered As A Racemic Mixtumentioning

confidence: 99%

“…S-(-)-VER has negative chronotropic and inotropic effects, delays atrioventricular node conduction and causes systemic and coronary artery vasodilatation. In contrast, a similar concentration of R-(+)-VER results in vasodilatation of the arterial and coronary vasculature, but is relatively devoid of direct cardiac effects (Mateus et al, 2007;Pagel et al, 1998). S-(-)-VER is 10-20 times more potent than R-(+)-VER in slowing the cardiac A-V conduction velocity in humans, dogs and rabbits (Lankford and Bai, 1995;Mateus et al, 2007).…”

Section: Ver Is a Chiral Drug That Is Administered As A Racemic Mixtumentioning

confidence: 99%

“…The versatility of polysaccharide stationary phases for the analytical-scale separation of racemic verapamil is well documented in the literature, with amylosebased chiral stationary phases being the most common (Shibukawa and Wainer, 1992;Mateus et al, 2007;Fieger and Blaschke, 1992). The Chiralpak® AD (10 cm x 1.0 cm I.D., 20 µm) column efficiently separated the verapamil enantiomers.…”

Section: Elution Profile and Chromatographic Parameters For The Racemmentioning

confidence: 99%

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Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

Cremasco

Santana²

2015

Braz. J. Chem. Eng.

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-Verapamil is a chiral drug that is marketed in its racemic form, but because of the pharmacological effects due to molecule's chirality, one of the enantiomers is more potent, and the other exhibits different activities of therapeutic interest. The preparative separation of the verapamil enantiomers was performed using a continuous Varicol unit operated on a scale of 1 g/day. Amylose tris(3,5-dimethylphenylcarbamate) functioned as the stationary phase, and n-hexane/isopropanol/ethanol mixtures were used as the mobile phase. Diethylamine was used as the additive. The enantiomeric purities were 93.0% for S-(-)-verapamil and 92.0% for R-(+)-verapamil in the raffinate and extract streams, respectively. The unit provided productivities of 0.18 kg of raffinate per day per kg of adsorbent and 0.20 kg of extract per day per kg of adsorbent when using a feed concentration of 12.5 g L -1 .

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Section: Ver Is a Chiral Drug That Is Administered As A Racemic Mixtumentioning

confidence: 96%

Section: Ver Is a Chiral Drug That Is Administered As A Racemic Mixtumentioning

confidence: 99%

Section: Ver Is a Chiral Drug That Is Administered As A Racemic Mixtumentioning

confidence: 99%

Section: Elution Profile and Chromatographic Parameters For The Racemmentioning

confidence: 99%

See 2 more Smart Citations

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

Cremasco

Santana²

2015

Braz. J. Chem. Eng.

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“…A análise dos enantiômeros do verapamil e norverapamil em plasma de ratos foi realizada de acordo com o método desenvolvido e validado em estudo anterior do grupo (MATEUS et al, 2007). O método emprega 100 µL de plasma, extração líquido-líquido, separação dos enantiômeros na coluna de fase quiral Chiralpak AD ® e análise por LC-MS-MS. …”

Section: Análise Dos Enantiômeros Do Verapamil E Norverapamil Em Plasunclassified

Influência da exposição inalatória a combustíveis automotivos na atividade do CYP3A, CPY2C e CYP2D em ratos tratados com fármacos quirais

Cardoso¹

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Influence of N‐hexane inhalation on the enantioselective pharmacokinetics and metabolism of verapamil in rats

et al. 2009

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Verapamil (VER) is commercialized as a racemic mixture of the (+)-(R)-VER and (-)-(S)-VER enantiomers. VER is biotransformed into norverapamil (NOR) and other metabolites through CYP-dependent pathways. N-hexane is a solvent that can alter the metabolism of CYP-dependent drugs. The present study investigated the influence of n-hexane (nose-only inhalation exposure chamber at concentrations of 88, 176, and 352 mg/m3) on the kinetic disposition of the (+)-(R)-VER, (-)-(S)-VER, (R)-NOR and (S)-NOR in rats treated with a single dose of racemic VER (10 mg/kg). VER and NOR enantiomers in rat plasma was analyzed by LC-MS/MS (m/z = 441.3 > 165.5 for the NOR and m/z 455.3 > 165.5 for the VER enantiomers) using a Chiralpak AD column. Pharmacokinetic analysis was performed using a monocompartmental model. The pharmacokinetics of VER was enantioselective in control rats, with higher plasma proportions of the (-)-(S)-VER eutomer (AUC(0-infinity) = 250.8 vs. 120.4 ng/ml/h; P < or = 0.05, Wilcoxon test). The (S)-NOR metabolite was also found to accumulate in plasma of control animals, with an S/R AUC(0-infinity) ratio of 1.5. The pharmacokinetic parameters AUC(0-infinity), Cl/F, Vd/F, and t(1/2) obtained for VER and NOR enantiomers were not altered by nose-only exposure to n-hexane at concentrations of 88, 176, or 352 mg/m3 (P > 0.05, Kruskal-Wallis test). However, the verapamil kinetic disposition was not enantioselective for the animals exposed to n-hexane at concentrations equal to or higher than the TLV-TWA. This finding is relevant considering that the (-)-(S)-VER eutomer is 10-20 times more potent than R-(+)-VER in terms of its chronotropic effect on atrioventricular conduction in rats and humans.

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Simultaneous analysis of the enantiomers of verapamil and norverapamil in rat plasma by liquid chromatography-tandem mass spectrometry

Cited by 12 publications

References 15 publications

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

Chromatographic Separation of Verapamil Racemate Using a Varicol Continuous Multicolumn Process

Influência da exposição inalatória a combustíveis automotivos na atividade do CYP3A, CPY2C e CYP2D em ratos tratados com fármacos quirais

Influence of N‐hexane inhalation on the enantioselective pharmacokinetics and metabolism of verapamil in rats

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