Abstract
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 μm, 50 x 2.0 mm) and pre-column SecurityguardTM 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.
Highlights
Nimodipine (Figure 1) is a dihydropyridine c a l cium channel blocker known for its preferential action on cerebral blood vessels (Kazda, Toward, 1982; Haws et al, 1983), but it is currently used to prevent and treat the ischemic damage caused by cerebral arterial spasm in subarachnoid hemorrhage (Dorhout Mees et al, 2007; Stachura et al, 2002)
Gas chromatography (GC) methods with electron-capture (Krol et al, 1984; Jackobsen, et al, 1986) and nitrogenphosphorus detection (Rosseel, Bogaert, Huyghens, 1990) were used to determine nimodipine in plasma, which can provide a lower limit of quantification (LLOQ) of 5 ng/mL, using 1 mL of plasma
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
Summary
Nimodipine (Figure 1) is a dihydropyridine c a l cium channel blocker known for its preferential action on cerebral blood vessels (Kazda, Toward, 1982; Haws et al, 1983), but it is currently used to prevent and treat the ischemic damage caused by cerebral arterial spasm in subarachnoid hemorrhage (Dorhout Mees et al, 2007; Stachura et al, 2002). The method described by Krol et al (1984) is sensitive and selective; it requires a large amount of plasma and elaborate and lengthy sample preparation. In all the reported methods above, plasma volume requirement was high, chromatographic run time was longer and sensitivity was inadequate for pharmacokinetic studies. 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. The analytical time was more than 30 min, which is not suitable for the analysis of a large number of biological samples
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