Simultaneous Assessment of the Intravenous and Oral Disposition of the Enantiomers of Racemic Nimodipine by Chiral Stationary- Phase High-Performance Liquid Chromatography and Gas Chromatography/Mass Spectroscopy Combined with a Stable Isotope Technique

Fischer, Christine; Schönberger, Frank; Mück, Wolfgang; Heuck, K.; Eichelbaum, Michel

doi:10.1002/jps.2600820305

Cited by 33 publications

(19 citation statements)

References 21 publications

(6 reference statements)

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“…Our results demonstrated, however, that the mean half-life of nimodipine for the two formulations tested was 27.83 h (test formulation) and 32.78 h (reference formulation). Such a discrepancy could be due to the greater sensitivity of our method, with a limit of quantification of 100 pg/mL, while values found in previous studies were in the range 0.24 to 5 ng/mL (Krol et al, 1984;Jackobsen et al, 1986;Rosseel et al, 1990;Qian, Gallo, 1992;Fischer et al, 1993;Yan et al, 1993;Mück, 1995;Aymard et al, 1998;Gualano et al, 1999;López et al, 2000;Blardi et al, 2002;Qiu et al, 2004;Zhonggui et al, 2004;Nirogi et al, 2006). This improved sensitivity enabled the determination of plasma drug concentrations up to 48 h after drug administration, which was not possible in other studies that allowed the measurement of plasma drug levels only up to 10 h after drug administration.…”

Section: Pharmacokinetic Studymentioning

confidence: 60%

“…The relatively longer run time for nimodipine registered by these analytical methods are not adequate for the analysis of a high number of samples. Fischer et al, 1993 developed a GC-MS method combined with chiral stationary phase HPLC for the separation and determination of nimodipine enantiomers, which had an LLOQ of 0.1 ng/mL, using 0.5 mL of plasma. However, the analytical time was more than 30 min, which is not suitable for the analysis of a large number of biological samples.…”

Section: Introductionmentioning

confidence: 99%

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Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Nascimento

Moraes

Bezerra

et al. 2010

Braz. J. Pharm. Sci.

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To develop and validate a rapid, specific and highly sensitive method to quantify nimodipine in human plasma using dibucaine as the internal standard (IS). The analyte and IS were extracted from plasma samples by liquid-liquid extraction using hexane-ethyl acetate (1:1 v/v). The chromatographic separation was performed on a Varian ® Polaris C18 analytical column (3 mm, 50 x 2.0 mm) and pre-column Securityguard TM C18 (4.0 x 3.0 mm) with a mobile phase of Acetonitrile-Ammonium acetate 0.02 ml/L (80:20v/v). The method had a chromatographic run time of 4.5 min and linear calibration curve over the range of 0.1-40 ng/mL (r > 0.9938). The limit of quantification was 100 pg/mL. Acceptable precision and accuracy were obtained for concentrations over the standard curve ranges. This validated method was successfully applied in determining the pharmacokinetic profile of nimodipine tablets of 30 mg administered to 24 healthy volunteers. The proposed method of analysis provided a sensitive and specific assay for nimodipine determination in human plasma. The time for the determination of one plasma sample was 4.5 min. This method is suitable for the analysis of nimodipine in human plasma samples collected for pharmacokinetic, bioavailability or bioequivalence studies in humans.Uniterms: Nimodipine/determination in plasma. Nimodipine/pharmacokinetic profile. Nimodipine/ quantitative analysis. Pharmacokinetics/method validation.Um método rápido, específico e sensível para quantificar nimodipino em plasma humano usando dibucaína como padrão interno (IS) é descrito. O analito e o IS foram extraídos das amostras de plasma por extração líquido-líquido usando hexano-acetato de etila (1:1 v/v). A separação cromatográfica foi realizada utilizando-se uma coluna analítica C18 Varian ® Polaris (3 mm, 50 x 2,0 mm) e uma pré-coluna Securityguard TM C18 (4,0 x 3,0 mm) e acetonitrila-acetato de amônia 0,02 mol/L (80:20 v/v) como fase móvel. O método apresentou tempo total de corrida de 4,5 min e curva de calibração linear com concentrações entre 0,1-40 ng/mL (r > 0,9938). O limite de quantificação foi de 100 pg/mL. Os valores de precisão e exatidão foram obtidos por meio da análise das amostras de controle de qualidade. A análise de uma única amostra de plasma foi realizada em 4,5 minutos. A metodologia validada foi aplicada na determinação do perfil farmacocinético do nimodipino, comprimido de 30 mg administrado em 24 voluntários saudáveis. O método para quantificar nimodipino em plasma é adequado para aplicação em estudos farmacocinéticos, biodisponibilidade e bioequivalência em humanos.

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Section: Pharmacokinetic Studymentioning

confidence: 60%

Section: Introductionmentioning

confidence: 99%

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Nascimento

Moraes

Bezerra

et al. 2010

Braz. J. Pharm. Sci.

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show abstract

“…15,18 Quality control samples for S-verapamil and R-verapamil were routinely assayed, with an intra-assay coefficient of variation of Ͻ4% and an interassay coefficient of variation of Ͻ9%. Urine samples were analyzed for verapamil and its metabolites (norverapamil, D-620, D-715, D-617, D-717, D-703) by HPLC as previously described.…”

Section: Analytical Methods For Determination Of Labeled and Unlabeledmentioning

confidence: 99%

Modulation by Dietary Salt of Verapamil Disposition in Humans

Darbar

Fromm²,

Dell’Orto³

et al. 1998

Circulation

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Background-The intestine is an increasingly well-recognized site of first-pass drug metabolism. In this study, we determined the influence of dietary salt on the steady-state disposition of verapamil, a drug that undergoes extensive first-pass metabolism. Methods and Results-Eight normal volunteers received 120 mg of racemic verapamil orally twice a day for 21 days. The disposition kinetics of verapamil enantiomers were determined after coadministration of intravenous deuterated verapamil with the morning oral dose on days 7, 14, and 21. Each study day was preceded by 7 days on a fixed-salt diet: in 5 subjects, the initial study was conducted during a low-salt (10 mEq/d) diet, the second study during a high-salt (400 mEq/d) diet, and the third during a low-salt diet, whereas in the other 3 subjects, the sequence of diets was reversed.

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“…HPLC with UV detection [10][11][12] and electrochemical detection [13] have a sensitivity of about 1 ng/ml in 1 ml plasma, but these methods are time-consuming (more than 10 min). Fischer et al [14] developed a GC−MS method combined with chiral stationary phase HPLC for the separation and determination of nimodipine enantiomers which had an LLOQ of 0.1 ng/ml using 0.5 ml plasma, but the analytical time was more than 30 min which was not suitable for the analyses of large amounts of biological samples. Mück [15] developed an LC−MS−MS method providing an LLOQ of 0.5 ng/ml in 1 ml plasma sample, but the method was also used for the quantification of nimodipine enantiomers.…”

Section: Introductionmentioning

confidence: 99%

Determination of nimodipine in human plasma by a sensitive and selective liquid chromatography–tandem mass spectrometry method

Qiu

Chen

et al. 2004

Journal of Chromatography B

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Simultaneous Assessment of the Intravenous and Oral Disposition of the Enantiomers of Racemic Nimodipine by Chiral Stationary- Phase High-Performance Liquid Chromatography and Gas Chromatography/Mass Spectroscopy Combined with a Stable Isotope Technique

Cited by 33 publications

References 21 publications

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Determination of nimodipine in plasma by HPLC-MS/MS and pharmacokinetic application

Modulation by Dietary Salt of Verapamil Disposition in Humans

Determination of nimodipine in human plasma by a sensitive and selective liquid chromatography–tandem mass spectrometry method

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