苯巴比妥钠注射液的分解产物

A major degradated product was obtained from sodium phenobarbital injection stored at room temperature or heated at 100℃ for a long time. It was identified by means of melting point, optical rotation, UV and IR spectrum, elemental analysis and paper chromatography to be dl-pheneturide irrespective of the source of sample.A search in the literature showed that this degradated product is a potent anticonvulsant.     

苯巴比妥钠注射液贮存期预测

<正> 我国药典(1985年版)收载注射用苯巴比妥钠为粉针剂。英、美药典为丙二醇与水的复溶媒溶液剂。现临床应用的注射剂多数为粉针剂型,但也有溶液制剂。 据文献报道笨巴比妥钠溶液的水解速度与温度,pH值有密切关系。10％水溶液于1℃条件下可保持60日无分解,而在39℃30日内可分解22％。若将苯巴比妥钠溶于有机溶剂的复溶媒中,使其降低介电常数,减低离子间反应速度,则可获得     

苯巴比妥钠注射液的稳定化

前两报研究证明,苯巴比妥钠注射液稳定性较差,贮存期短。根据化学动力学研究,降低溶液的pH值可明显增加其稳定性。但经我们计算,25℃时10％的苯巴比妥钠水溶液当pH值降至9.18时即析出苯巴比妥沉淀。显然,通过降低pH值的途径使其稳定受到限制。     

10%苯巴比妥钠注射液贮存期预测

苯巴比妥钠系缩丙二酰脲衍生物,不稳定易加水分解。关于苯巴比妥的水解动力学和稳定性研究报道较多,但对10％苯巴比妥钠丙二醇(60％)注射液的贮存期预测,未见报道。作者根据Arrhenius定律用恒温加速试验法,然后外推至室温预测贮存期。并用回归方程处理实验数据。     

10%苯巴比妥钠注射液贮存期预测

The shelf-life of 10% sodium phenobarbital injection(containing propylene glycol 60%) has been predicted by accelerated stability test with the classical isothermal method (at 100, 90, 80 and 70℃). The data was treated with regressive calculation, and the shelf-life calculated with three different methods (regressive calculation, average activation energy calculation and graphical plotting).The values obtained from these three methods were approximately equal, and also coincided with the value obtained from samples reserved for observation at room temperature. The shelf-life was 1.05 years at 25℃, and 2.03 years at 20℃.     

苯巴比妥钠注射液细菌内毒素检查法标准研究

目的：苯巴比妥钠注射液现有检验标准“国家药品标准WS1-XG-058-2011”无细菌内毒素或热原检查项目,一方面给临床造成很大的安全隐患,另一方面也不符合“注射剂安全检查法应用指导原则” _[1]。建立该品种的细菌内毒素检查方法非常必要。方法：依照《中国药典》2015年版四部1143检查法_[2],采用凝胶限量法对两个厂家4个批次的苯巴比妥钠注射液进行干扰试验,拟定细菌内毒素检查限值;另取两个厂家8个批次的苯巴比妥钠注射液按拟定细菌内毒素检查限值采用凝胶法和动态浊度法对其进行定性和定量检验,验证方法的可行性。结果：根据干扰试验结果,参考USP40-NF35.2017苯巴比妥钠注射液细菌内毒素检验_[3],拟定每1mg苯巴比妥钠中含细菌内毒素的量应小于0.3EU;采用凝胶法和动态浊度法对两个厂家8个批次的苯巴比妥钠注射液按细菌内毒素的限值小于0.3EU.mg-1 进行检查,结果均符合规定。结论：该实验建立的细菌内毒素检查法适用于苯巴比妥钠注射液。拟定标准：取本品,依法检验(《中国药典》2015年版四部1143),每1mg苯巴比妥钠注射液中含细菌内毒素的量应小于0.3EU.与USP40-NF35.2017苯巴比妥钠注射液细菌内毒素检验结果一致。     

HPLC法测定苯巴比妥钠注射液有关物质及含量

目的:建立苯巴比妥钠注射液中含量和有关物质测定的HPLC方法.方法:色谱柱为Rainbow彩虹C18(4.6 mm×250mm,5 μm),流动相为pH 4.5缓冲盐(称取三水合醋酸钠6.6 g和3 mL冰醋酸,加水至1 000 mL,必要时用冰醋酸调节pH值至4.5±0.1).甲醇(3∶2),检测波长为254 nm,按外标法以峰面积进行计算.结果:苯巴比妥钠在393～1 967 mg·L-1浓度范围内线性关系良好,r=1.000 0;平均回收率为100.2%,RSD=1.0%.专属性试验结果表明本品在热、酸、碱、氧化和光照条件下均有不同程度的降解,各降解产物峰与主成分峰均能达到较好的分离.结论:该法专属性好,简捷、快速、准确,适用于苯巴比妥钠注射液含量测定及有关物质检查.     

HPLC法测定苯巴比妥钠注射液中苯巴比妥含量及5种有关物质

摘要：目的:建立苯巴比妥钠注射液中苯巴比妥含量及5种有关物质的HPLC法。方法:采用Phenomenex Luna C18（250mm×4.6 mm,5μm）色谱柱以醋酸钠溶液（取醋酸钠6.6 g、3 ml冰醋酸至1 000 ml水中,调pH至4.5±0.1）-甲醇（60:40）为流动相流速为1.0 ml·min-1,检测波长为220 nm,柱温为30℃,进样量20μl。结果:苯巴比妥的线性范围为9.97～997.00μg·ml-1（r=1.000 0）,杂质A、杂质B、杂质C、苯丁酰脲、巴比妥酸的线性范围为1～1 000μg·ml-1（r值范围0.999 9～1.000 0）;苯巴比妥的检出限为2μg·ml-1;杂质A检出限为0.2μg·ml-1;杂质B、苯丁酰脲、巴比妥酸检出限为0.5μg·ml-1;杂质C检出限为1μg·ml-1。苯巴比妥、杂质A、杂质B、杂质C、苯丁酰脲、巴比妥酸的回收率分别为100.56%,96.21%,99.39%,99.46%,101.54%,102.83%,RSD分别为0.36%,0.86%,0.37%,0.32%,0.53%,0.64%（n=9）。结论:该方法重复性好,专属性强,可以更加有效控制苯巴比妥钠注射液的质量。     

苯巴比妥钠致皮肤过敏2例

1 病历报告　病例1,患者男性、38岁、住院号107552,因外伤致腰背、右肩肿痛,活动障碍5h于2000年3月11日入住本科.诊断：右肱骨外科颈粉性骨折并肩关节脱位,腰1椎体压缩性骨折.经过检查,术前准备完善后定于3月17日上午在臂丛神经阻滞麻醉下行右肱骨外科颈粉碎性骨折、肩关节脱位切开复位内固定术.术前一般情况好,青霉素、普鲁卡因药物皮肤过敏试验阴性,按医嘱术前30min给苯巴比妥钠0.1g肌肉注射,约5min后,病人即感尿道口、指（趾）间皮肤瘙痒,局部皮肤稍红,未见皮疹及红斑.约15min后,     

反相高效液相色谱法测定注射用美洛西林钠含量

目的:建立反相高效液相色谱法测定注射用美洛西林钠含量。方法:采用SPHERI—5 RP—18色谱柱,乙腈—醋酸盐缓冲液(20:80,pH5.0±0.1)为流动相,流速为0.95ml/min,检测波长为230mm,乙酰苯胺为内标物。结果:美洛西林钠在0.163～0.817mg/ml范围内线性良好(r=0.9998),平均回收率(n=6)为99.78％(RSD=0.62％)。结论:本方法简便,快速,准确,可靠。     

电位滴定-水溶液银量法测定盐酸林可霉素注射液中氯化钠的含量

目的　建立测定盐酸林可霉素注射液中氯化钠含量的方法。方法　电位滴定 -水溶液银量法结合HPLC外标法。在水溶液中 ,以Mettler复合银电极指示 ,用 0 .1mol·L- 1 硝酸银液滴定至电位发生突跃 ;测得结果扣除注射液中林可霉素盐酸盐对硝酸银滴定液的本底消耗 ,即得注射液中氯化钠的纯含量。结果　林可霉素A、B组分总含量在 6 .0～ 1 2 0 .2mg·ml- 1 范围内 ,溶液中林可霉素总浓度与硝酸银滴定液的消耗体积有良好的线性关系 ,r=0 .9999;方法重复性好 (RSD =0 .1 % ,n =5) ;准确度高 ,回收率为 99.2 % (RSD =0 .5 % ,n =6) ,加样回收率为1 0 0 .2 % (RSD =0 .4 % ,n =6)。结论　方法准确、便捷、适用 ,可准确测定盐酸林可霉素注射液中氯化钠的含量     

苯巴比妥钠诱导小鼠引起的记忆障碍及奥丹色隆的拮抗作用

小鼠每组各１０只，ｉｐ７５ｍｇ·ｋｇ－１·ｄ－１苯巴比妥钠连续６ｄ，２ｗｋ后，采用Ｙ型迷津测定其学习能力，结果表明用药组１０次中的错误次数为６．４±ｓ１．５，明显多于生理盐水组的２．６±ｓ１．３（Ｐ＜０．０１）。而与ｉｐ１．５ｍｇ·ｋｇ－１东莨菪碱组相近（５．７±ｓ１．６）。预先加脑复康１５０ｍｇ·ｋｇ－１ｐｏ或奥丹色隆１０μｇ·ｋｇ－１ｉｐ，均能改善苯巴比妥钠引起的记忆损害。采用小鼠跳台法结果也类似。本研究结果证明苯巴妥钠引起记忆损害可出现在用药２ｗｋ后，且其机理可涉及ＧＡＢＡ能和５－ＨＴ能递质。     

复方颠茄片中苯巴比妥的差示分光光度测定

利用苯巴比妥在碱液中由酮式转变为烯醇式的特性，采用差示分光光度法测定复方颠茄片中苯巴比妥的含量，结果准确、快速。     

ALPRAZOLAM HYDROXYLATION BY MOUSE LIVER MICROSOMES IN VITRO: THE EFFECT OF AGE AND PHENOBARBITAL INDUCTION

The effects of age on hepatic microsomal enzyme induction were studied in male CD-1 mice. Six week old and 1 year old animals were treated with either phenobarbital (80 mg kg⁻¹) or saline once daily for 3 d. Twenty-four hours after the last treatment, animals were sacrificed and livers were harvested. Hepatic microsomal fractions were isolated and incubated with alprazolam, a triazolobenzodiazepine metabolized by cytochrome P-450-3A isoforms in humans. Metabolites were identified and quantitated by HPLC. All microsomal preparations produced two principal metabolites (α-OH- and 4-OH-alprazolam) while microsomes from phenobarbital-treated animals also produced a third metabolite (α, 4-dihydroxyalprazolam). V_max , K_m , and intrinsic clearance (V_max/K_m ratio) for both α-OH- and 4-OH-alprazolam in the saline-treated control animals were not significantly different between age groups. V_max and intrinsic clearance for both metabolites were more than three times greater in phenobarbital-treated animals than in the control mice (p <0·001). Age did not influence the extent of induction, and both pathways were induced to approximately an equal extent. Thus the present in vitro study of liver microsomal preparations from male CD-1 mice does not delineate a mechanism for impaired alprazolam clearance in aging organisms in vivo. There is no evidence that age alters susceptibility to induction by phenobarbital. © 1997 by John Wiley & Sons, Ltd.     

月桂氮酮促进苯巴比妥栓剂直肠吸收的最佳浓度研究

采用反相HPLC测定苯巴比妥血药浓度,用抛物线拟合法建立了栓剂中月桂氮(艹卓)酮(1)为不同浓度时苯巴比妥血药浓度-时间曲线下面积的数学模型,用此模型求得了1促进苯巴比妥栓剂直肠吸收的最佳浓度为3.1％。实验证明,3％1可使直肠24h内对苯巴比妥的吸收作用增加到238％,有明显的促进。