Phenazopyridine associated acute interstitial nephritis and review of literature

Phenazopyridine is a urinary analgesic; commonly seen side-effects of this drug include, orange discoloration of urine, methemoglobinemia, yellowish skin discoloration, hepatitis and acute renal failure. Various case reports with phenazopyridine associated acute renal failure secondary to acute tubular necrosis have been reported in the literature. Acute kidney injury in these patients is caused by either direct injury to renal tubular epithelial cells or secondary to pigment induced nephropathy from hemolytic anemia. Hypoxic injury from phenazopyridine-induced methemoglobinemia has been well documented. We report a case of biopsy proven acute interstitial nephritis, associated with therapeutic doses of phenazopyridine without any evidence of methemoglobinemia or other mechanism of renal injury. Clinicians should be aware of the toxicity of this commonly used drug and should look closely for signs of renal insufficiency. Identifying and stopping the offending medication stays as the first step, but recent studies indicate that early steroid administration improves renal recovery, as well as decreasing the risk of progression to chronic kidney disease with fibrosis and consequent permanent renal damage.     

盐酸非那吡啶的合成及其热稳定性初步研究

目的研究盐酸非那吡啶的制备工艺及其热稳定性。方法以苯胺为原料,经重氮化、偶合、中和、成盐得盐酸非那呲啶;用热重分析法(TG)和差示扫描量热法(DSC)对其热稳定性进行初步研究。结果本工艺路线4步总收率为71.5%;在氮气氛(氮气流量为20 mL.min-1)、10 K.min-1的升温条件下,将盐酸非那吡啶加热到235℃才开始发生剧烈分解,至287.4℃时,有50.79%的盐酸非那呲啶发生分解。结论本制备方法简单,适合于大量制备。本品的热稳定性较好。     

Development and validation of a gas chromatography-mass spectrometry method for the determination of phenazopyridine in rat plasma: application to the pharmacokinetic study

Phenazopyridine hydrochloride is a strong analgesic used in the treatment of urinary tract infections. The aim of the present study was to develop a procedure based on gas chromatography-mass spectrometry (GC-MS) for the analysis of phenazopyridine in rat plasma. The method was set up and adapted for the analysis of small biological samples taken from rats. Biological samples were extracted by liquid-liquid extraction. The extraction agent was ethyl acetate. The samples were separated by GC on a DB-5MS analytical column and determined by a quadrupole mass spectrometer detector operated under selected ion monitoring mode. Excellent linearity was found between 0.01 and 1.00 microg/ml (r = 0.9991, n = 9) for plasma samples. The limit of detection (LOD) was 0.3 ng/ml. Within-day and between-day precisions expressed as the relative standard deviation (RSD) for the method were 1.83-4.91% and 2.12-4.76%, respectively. The recoveries for all samples were >90%. The main pharmacokinetic parameters obtained were T(max) = (0.35+/-0.01) h, C(max) = (0.396+/-0.079) microg/ml, AUC = (0.373+/-0.065) h microg/ml and CL = (94.2+/-5.9) ml/g/h. The results presented here clearly indicate that this proposed method could be applicable to investigate the pharmacokinetic of phenazopyridine in rats after administration. (c)     

盐酸非那吡啶有关物质及含量检测方法的改进

目的：优化和改进盐酸非那吡啶有关物质及含量的检测方法。方法：采用Phenomenex Luna C18（2）柱（4.6 mm×250 mm,5μm）,以磷酸盐缓冲液（取磷酸氢二铵2.64 g,加水900 mL溶解后,用磷酸调节pH值至3.0,加水使成1000 mL）-甲醇（50∶50）为流动相,流量1.0 mL· min^-1,检测波长240 nm,柱温35℃。结果：盐酸非那吡啶与已知杂质2,6-二氨基吡啶、苯胺能有效分离。盐酸非那吡啶在0.504～25.220μg· mL^-1浓度范围内呈良好线性关系（r＝1.0000）,检出限为1.0 ng;2,6-二氨基吡啶在0.213～5.315μg · mL^-1浓度范围内呈良好线性关系（ r＝1.0000）,检出限为0.2 ng;苯胺在0.103～2.572μg · mL^-1浓度范围内呈良好线性关系（ r＝0.9999）,检出限为1.9 ng。结论：改进后的方法更能有效控制盐酸非那吡啶的质量。     

随机共振应用于人血浆中非那吡啶弱色谱信号的定量分析

目的运用随机共振法对湮没在噪声中的弱色谱峰进行定量分析。方法基于随机共振理论，通过优化系统参数和Runge-Kutta方法来提高信噪比的方式建立了能提高色谱检测限的随机共振算法，并应用于HPLC/UV法定量检测人血浆中的非那吡啶浓度。同时将该方法与HPLC/MS法进行了比较。结果实验数据表明非那吡啶的浓度与响应值之间的线性关系良好。通过两种方法分别测得的受试者的血药浓度数据说明了这两种方法差异无显著性意义。结论该方法是可行的。