Application of oxidants to the spectrophotometric determination of amlodipine besylate in pharmaceutical formulations

Three new spectrophotometric methods for the determination of amlodipine besylate have been proposed. The first two methods, i.e. A and B, are based on the oxidation of the drug with Fe(III) and the estimation of Fe(II) produced after chelation with either 1,10-phenanthroline or 2,2'-bipyridyl at 500 and 515 nm, respectively. The Beer's law was obeyed in the concentration ranges of 2-10 and 4-14 microg ml(-1) with molar absorptivity of 2.9 x 10(4) and 2.7 x 10(4) l mol(-1) cm(-1) for methods A and B, respectively. The third procedure depends on the interaction of amlodipine besylate with ammonium heptamolybdate tetrahydrate, which resulted in the formation of molybdenum blue (lambda(max) 825 nm). The linear dynamic range and the molar absorptivity values were found to be 15-59 microg ml(-1) and 1.8 x 10(4) l mol(-1) cm(-1), respectively. The results of the proposed procedures were validated statistically and compared with those obtained by the reference method. The proposed methods were applied successfully to the determination of amlodipine besylate in commercial tablets.     

Rocuronium and cisatracurium-positive skin tests in non-allergic volunteers: determination of drug concentration thresholds using a dilution titration technique

BACKGROUND: Muscle relaxants are believed to be responsible for 2/3 of the cases of anaphylactic reactions during anesthesia. This assumption is based mainly on positive skin tests obtained in individuals that have experienced anesthesia-related anaphylaxis. A positive skin test is supposed to be associated with mast cell degranulation of vasoactive amines. In the present study we tested the frequency of positive skin tests with two commonly used muscle relaxants, rocuronium and cisatracurium, in a selected group of volunteers with low potential for allergic reactions. METHODS: Thirty healthy volunteers without known allergy or previous exposure to muscle relaxants were studied. Low potential for allergic reactions was determined prior to inclusion in the study, using various allergy tests. Each individual was tested with intradermal and skin prick tests, and molar drug concentration thresholds for positive skin reactions were determined using a dilution titration technique. The presence or absence of mast cell degranulation was tested by electron microscopic investigation of skin biopsies obtained from positive and negative skin reactions. RESULTS: None of the volunteers had a positive skin prick test. More than 90% of the volunteers had a positive intradermal test with both rocuronium and cisatracurium. The highest molar drug concentration that was not associated with a positive intradermal test was 10(-6) M (rocuronium) and 10(-7) M (cisatracurium), equivalent to vial dilution 1 : 1000 for both drugs. In none of the volunteers was mast cell degranulation detected. CONCLUSION: Non-mast-cell-mediated positive intradermal skin reactions are frequently occurring with rocuronium and cisatracurium, even at vial dilution 1 : 1000. A clinically applicable test technique is needed that is able to separate positive skin tests associated with mast cell degranulation from non-mast-cell-mediated reactions.     

苯磺酸左旋氨氯地平联合硝酸甘油治疗高血压性脑出血术后病人的临床观察

目的：研究苯磺酸左旋氨氯地平联合硝酸甘油治疗高血压性脑出血术后病人的疗效和安全性。方法：40例高血压性脑出血术后患者随机分成研究组和对照组，各20例。研究组苯磺酸左旋氨氯地平联合硝酸甘油控制血压，对照组采用硝酸甘油治疗。结果：两组患者肝功、肾功、血糖及甘油三酯无明显影响，不良反应相似。与对照组比较，研究组心率无明显变化，硝酸甘油用量明显减少。结论：苯磺酸左旋氨氧地平联合硝酸甘油治疗高血压性脑出血术后病人的疗效可靠，安全性高。     

不同剂量顺苯磺酸阿曲库铵在神经外科全麻插管反应的观察

目的：观察不同剂量顺苯磺酸阿曲库铵用于神经外科手术全麻诱导后行气管插管时的心血管反应,探讨其最佳的全麻诱导剂量.方法：将60例择期行脑部脑肿瘤手术的患者随机均分为I-III组,15～65岁,质量平均40～80kg,ASAI-III.全麻诱导均采用咪唑安定0.03～0.05mg/kg,芬太尼4μg/kg,顺苯磺酸阿曲库铵剂量分别为0.15mg/kg（S1）,0.20mg/kg（S2）,0.30mg/kg（S3）,丙泊酚1～2mg/kg.并于给药5min后行气管插管,分别记录诱导前2min（T0,基础值）、插管前1min（T1）、插管后1min（T2）,3min（T3）,5min（T4）无创血压收缩压（SBP）、舒张压（DBP）、MAP、心率（HR）的变化.结果：所有患者均于给药5min后完成气管插管,插管条件达到1级47例（78.3%）,2级13例（21.7%）.S1组患者气管插管后血流动力学较诱导前明显增高,呈一过性; S2组患者气管插管后血流动力学较诱导前轻度增高; S3组患者气管插管后血流动力学较诱导前无明显变化.结论：麻醉诱导时顺苯磺酸阿曲库铵0.3mg/kg能有效减轻气管插管引起的应激反应并能缩短气管插管起效时间,用于颅脑肿瘤手术患者可能有利于减少气管插管引起的心脑血管意外情况的发生.     

培哚普利与苯磺酸氨氯地平联合治疗原发性高血压的疗效观察

目的探讨培哚普利与苯磺酸氨氯地平联合治疗原发性高血压的疗效。方法将80例原发性高血压患者随机分为治疗组和对照组,治疗组40例在应用培哚普利的基础上加用苯磺酸氨氯地平片,对照组40例采用培哚普利,观察两组药物对高血压的疗效。结果治疗组总有效率90.0%,对照组总有效率77.5%,两组比较差异有统计学意义(P0.05)。结论培哚普利与苯磺酸氨氯地平联合治疗高血压疗效肯定、不良反应少,值得推广。     

离子对高效液相色谱荧光法测定人血浆中顺式阿曲库铵的浓度

目的:建立反相离子对高效液相色谱荧光法测定人血浆中顺式阿曲库铵浓度。方法:酸化的血浆样品采用乙腈沉淀蛋白处理,取上清液进样分析。色谱柱为Agilent Eclipse C18(150 mm×4.6 mm,5μm),流动相为1.5%三氟乙酸-乙腈(55∶45),流速0.5 mL·min-1,荧光的激发波长为280 nm,发射波长为320 nm。结果:顺式阿曲库铵在12.4～4960.0 ng·mL-1范围内线性关系良好(r=0.9998),检测限为1.24 ng·mL-1,平均提取收率为85.1%～88.5%,平均方法回收率为98.3%～102.1%,日内、日间RSD均<3.4%。结论:本方法操作简便、灵敏度高、专一性强、结果可靠,可满足临床检测和药代动力学研究的需要。     

顺式阿曲库铵和罗库溴铵在老年患者中的药效学比较

目的:观察单次静脉注射不同剂量的顺式阿曲库铵在老年患者中的药效学变化,并与壮年患者和罗库溴铵比较,为顺式阿曲库铵在老年患者麻醉中的应用提供参考。方法:择期全麻乳腺手术患者100例,根据年龄分为老年组(Ⅰ组)和壮年组(Ⅱ组),每组再分成4个亚组:罗库溴铵组(Ⅰ1,Ⅱ1)、顺式阿曲库铵2×ED95组(Ⅰ2,Ⅱ2),3×ED95组(Ⅰ3,Ⅱ3)和4×ED95(Ⅰ4,Ⅱ4),共8组。肌肉松弛监测采用4个成串刺激(train-of-four,TOF)。肌肉松弛效应观察指标包括:起效时间、TOF无反应期、T1恢复到25%,50%和75%的时间以及恢复指数。结果:老年组顺式阿曲库铵的起效时间稍长于壮年组,但差异无统计学意义;老年组顺式阿曲库铵的TOF无反应期、T1恢复到25%,50%和75%的时间及恢复指数均稍长于壮年组,但差异无显著性。老年组罗库溴铵起效时间明显长于其壮年组(P<0.05),且老年组肌肉松弛效应恢复的各项参数也均明显长于壮年组(P<0.05)。顺式阿曲库铵的肌松恢复指数在各组之间的差异无统计学意义。结论:对于女性而言,增龄对单次静脉注射顺式阿曲库铵的药效学无明显影响,对单次静脉注射罗库溴铵的药效学有显著影...     

反相高效液相色谱法测定苯磺酸氨氯地平胶囊的含量和有关物质

目的建立测定苯磺酸氨氯地平胶囊中苯磺酸氨氯地平含量及有关物质的反相高效液相色谱(RP-HPLC)法。方法采用HypersilBDS柱(200 mm×4.6 mm,5μm),以0.01 mol/L磷酸氢二钾溶液(含0.7%三乙胺,磷酸调pH=4.0±0.1)-乙腈(70∶30)为流动相,流速为1.0 mL/min,柱温为30℃,检测波长237 nm。结果苯磺酸氨氯地平峰和相邻杂质峰可达到有效分离(R>1.5)。苯磺酸氨氯地平质量浓度在5.0～50.0μg/mL范围内与峰面积线性关系良好(r=0.999 9,n=5);低、中、高3种质量浓度的平均回收率分别为99.17%,100.03%,99.85%,RSD分别为1.21%,0.87%,1.06%(n=3);方法的精密度和重复性良好,RSD均小于2%。结论该方法准确、简便、快速,适用于苯磺酸氨氯地平胶囊的质量控制。     

胸科手术中丙泊酚-七氟烷静吸复合麻醉对顺式阿曲库铵肌松效应的影响

目的观察丙泊酚-七氟烷静吸复合麻醉在胸科手术中对顺式阿曲库铵肌松效应的影响。方法选择择期胸科手术（包括肺叶切除和食管癌切除术）64例患者,ASAⅠ或Ⅱ级,年龄46~72岁,随机分为丙泊酚-七氟烷静吸复合麻醉组32例（七氟烷组）和丙泊酚-芬太尼静脉麻醉组32例（对照组）。麻醉期间监测有创桡动脉血压,心率和脑电双频指数（BIS）,使BIS维持在40~60,使用加速度肌松监测仪刺激前臂尺神经,观察拇内收肌的收缩反应,记录顺式阿曲库铵的起效时间、无反应时间、肌松维持时间以及恢复指数等指标。结果所有患者术中生命体征平稳,顺式阿曲库铵的起效时间、无反应时间以及T125%时间差异无统计学意义,但七氟烷组25%四个成串刺激（TOFr）恢复时间、恢复指数以及拔管时间明显延长（P〈0.05）。结论七氟烷明显增强顺式阿曲库铵肌松作用。