Development of a LC-ESI-MS3 method for determination of nitrendipine in human plasma

A novel and sensitive method utilizing high performance liquid chromatography coupled with electrospray ionization source tandem mass spectrometry (LC-ESI-MS³) was developed for the first time in order to analyze nitrendipine in human plasma samples. Human plasma samples were prepared by protein precipitation with acetonitrile and well resolved on a 100 mm reversed-phase column in gradient elution with 0.05% (v/v) formic acid in acetonitrile as the mobile phase. Determination was performed in MS³ scan mode for nitrendipine and in the multiple reaction monitoring (MRM) mode for nimodipine (internal standard). This method, having a lower limit of quantification (LLOQ) of 0.05 ng/mL when using a 100 μL sample aliquot (5 pg/sample), is acceptable for calibration of the linearity and repeatability and is of better sensitivity than the reported methods (>0.25 ng/mL). The major advantages of the method are that small sample volume (100 μL) is required, simple sample processing technique, high sensitivity and excellent selectivity is guaranteed by the MS³ detection. The proposed validated method has been successfully applied to a clinical study on nitrendipine.     

Differential roles of dihydropyridine calcium antagonist nifedipine, nitrendipine and amlodipine on gentamicin-induced renal tubular toxicity in rats

In the present study, we investigated the antioxidative potencies of dihydropyridine calcium antagonists prototype nifedipine, the second generation drug nitrendipine, and the long acting, third generation drug amlodipine on gentamicin-induced renal tubular toxicity in Sprague–Dawley rats. In addition, we analyzed the relationship between renal tubular cell apoptosis and the antioxidative properties of these dihydropyridine calcium antagonists. Results showed that treatment with gentamicin alone caused significant changes in the levels of urinary protein, urinary N-acetyl-beta-d-glucosaminidase, serum creatinine, and blood urea nitrogen. Nifedipine and amlodipine effectively reversed the effect of gentamicin on these parameters. In contrast, nitrendipine either had no effect or worsened gentamicin-induced changes in the levels of urinary protein, urinary N-acetyl-beta-d-glucosaminidase, serum creatinine, and blood urea nitrogen. Furthermore, gentamicin treatment caused significant increases in the levels of malondialdehyde, nitric oxide, nitric oxide synthase and significant decreases in the levels of reduced glutathione, glutathione-S-transferase, and superoxide dismutase in kidney tissues. These effects were dramatically reduced by nifedipine and amlodipine but not affected by nitrendipine. In addition to the biochemical changes, histopathological studies showed that gentamicin caused structural damages in the kidneys; renal tubular cell apoptosis, a decrease in Bcl-2 expression and an increase in Bax expression were observed in all rats treated with gentamicin, nifedipine and amlodipine effectively reversed the effect of gentamicin while nitrendipine worsened them. In conclusion, this study clearly indicated that nifedipine and amlodipine protected against gentamicin-induced nephrotoxicity while nitrendipine had little effect, or even worsened.     

尼群地平对氯氮平血药浓度及疗效的影响

[目的]探讨尼群地平对氯氮平血药浓度及疗效的影响。[方法]将长期住院精神分裂症伴高血压,且一直单一服用氯氮平治疗的70例患者,随机分为两组,对照组35例延用氯氮平治疗(200～500mg/d),研究组35例在延用氯氮平(剂量不变)的同时,合用尼群地平(20～30mg/d)治疗,治疗12周,以阳性症状与阴性症状量表(PANSS)评定疗效,用高效液相色普法(HPLC)测定氯氮平稳态血药浓度。[结果]合用尼群地平治疗组(研究组),在第8周末、12周末,氯氮平血药浓度升高,差异有统计学意义(P﹤0.05),12周末PANSS总分、阳性症状评分和阴性症状评分均有下降,差异有统计学意义(P﹤0.05)。[结论]尼群地平合用氯氮平治疗精神分裂症伴高血压患者时,会影响到氯氮平的血药浓度升高,但不影响其疗效。