HPLC法测定孟鲁司特钠片中孟鲁司特钠的含量

目的:对孟鲁司特钠片中孟鲁司特钠含量进行测定,建立制剂质量控制方法。方法:采用高效液相色谱法,LC-10AT高效液相色谱仪;色谱柱为Ultimate Phenyl(250 mm×4.6 mm,5μm);以水-乙腈-三氟乙酸(300∶200∶1)为流动相;检测波长为220 nm;柱温为室温;流速为1 ml·min-1;紫外检测波长为220nm;进样量为20μL。结果:孟鲁司特钠在0.04~0.32mg/m L浓度范围线性关系良好(r=0.9997)。结论:该法简便、快捷、结果准确、重复性好,可用于孟鲁司特钠片的质量控制。     

孟鲁司特钠的少见不良反应

孟鲁司特钠因其耐受性好,安全范围大,不良反应轻微而被临床广泛应用于儿童和成人哮喘的预防和长期治疗中。其临床试验资料也显示,孟鲁司特钠总的不良反应发生率与安慰剂相似,但随着临床实践的不断应用,相继出现各系统不良反应,包括精神系统紊乱,肝损害,肾功能损害,皮肤组织损害等等。虽然上述报道并不多见,但仍应引起广大医务工作者关注。     

孟鲁司特钠治疗儿童腺样体肥大的疗效观察

目的评估孟鲁司特钠治疗儿童腺样体肥大的鼻塞、打鼾、张口呼吸、夜间憋醒等临床症状的疗效。方法 53例3~8岁患腺样体肥大儿童,分为治疗组和手术组。观察治疗组治疗后3、6个月鼻塞、打鼾、张口呼吸、夜间憋醒的评分变化与手术组进行比较。结果治疗组治疗6个月后鼻塞、打鼾、张口呼吸、夜间憋醒改善程度和手术组无明显差异(P>0.05)。结论孟鲁司特钠治疗小儿腺样体肥大患儿的鼻塞、打鼾、张口呼吸、夜间憋醒等临床症状疗效显著。     

孟鲁司特钠致精神异常1例

患儿,男,5岁. 因反复咳嗽、气喘2 a再发3 d,于2009年5月来我院就诊. 既往无药物致变态反应史. 体检:体温36 ℃,双肺呼吸音粗,可闻及哮鸣音,诊断:支气管哮喘. 给予口服孟鲁司特钠咀嚼片5 mg, qd,晚上服;阿奇霉素0.15 g,qd;盐酸丙卡特罗片16.7 μg(规格:每片25 μg,2/3片),bid;布地奈德雾化混悬液1 mL;特布他林雾化液1 mL雾化吸入,bid. 2 d后患儿咳嗽、气喘明显减轻,但患儿出现大笑、大喊、打人、咬人等精神异常表现,因孟鲁司特钠有神经兴奋的不良反应,故暂停孟鲁司特钠咀嚼片,其他治疗不变. 2 d后患儿精神样症状消失,共治疗5 d后,停阿奇霉素及雾化吸入,患儿夜间仍咳嗽,再次口服孟鲁司特钠5 mg,当晚患儿再次出现大叫、大喊、大笑、打人、咬人等症状,立即停药,2 d后患儿精神症状消失,随访0.5 a,患儿再未出现类似症状. 2次精神样症状出现均未使用镇静类药物.     

孟鲁司特钠片微生物限度检查方法的验证

目的建立孟鲁司特钠片的微生物限度检查法,并对方法进行验证。方法采用离心集菌加薄膜过滤法,冲洗量为500ml。结果验证试验中各种菌的回收率均大于70％。结论该方法有效可行,可用于该品种的微生物限度检查。     

孟鲁司特钠咀嚼片细菌计数检查方法的比较与优化

目的:优化孟鲁司特钠咀嚼片细菌计数检查方法。方法:用两种稀释剂分别制备供试液,按2010年版《中国药典》进行回收率试验,比较不同计数方法回收率的高低,以选择该药品最佳的细菌计数方法。结果:添加0.5%大豆卵磷脂和4%聚山梨酯80的稀释剂可去除孟鲁司特钠咀嚼片的抗菌活性,细菌计数检查方法为常规法回收率可达70%以上;未添加中和剂组细菌计数检查方法为常规法回收率低于70%,需用1∶1 000稀释级常规法才能使回收率达到70%以上。结论:采用稀释剂中添加0.5%大豆卵磷脂和4%聚山梨酯80法可优化孟鲁司特钠咀嚼片的细菌计数检查方法。     

孟鲁司特钠片致皮疹

1例51岁女性患者，有过敏史，因支气管哮喘，在吸入布地奈德的同时，口服孟鲁司特钠10mg／d。服药第3天，四肢出现皮疹，伴瘙瘁，立即停服孟鲁司特钠，继续使用布地奈德，给予氯雷他定10mg／d口服。3d后，皮疹减轻，1周后皮疹消退。     

孟鲁司特钠咀嚼片相关双上肢震颤

1例72岁男性患者,因慢性支气管炎急性发作给予头孢哌酮-他唑巴坦2 g加入5%葡萄糖注射液250 ml,2次/d静脉滴注,共8 d;溴己新4 mg,2次/d静脉滴注,共15 d;氨茶碱0.1 g,1次/8 h口服,共17 d;孟鲁司特钠咀嚼片2片(每片10 mg),每晚口服1次,共16 d。第17天患者出现双上肢震颤,以手指部为甚,考虑为孟鲁司特钠咀嚼片所致,遂停用该药。停用后未再出现双上肢震颤。     

孟鲁司特钠咀嚼片致耳痛2例

患儿男,6岁。因夜间多次阵发性咳嗽出现呕吐、哮鸣音,2012年10月1日入湖南湘雅医院门诊治疗,诊断为过敏性咳嗽,给予孟鲁司特钠咀嚼片5mg/晚。服药后当天晚,咳嗽缓解,继续服药患儿咳嗽症状控制。10d后母亲见其用长长的纸卷塞在耳内,问其原因,说是耳痛,母亲并未引起重视,医嘱需服药半年,考虑到孩子咳嗽好转,同时畏惧药物说明书中的不良反应,即停药。一个月后,患者又出现夜间阵发性咳嗽,伴呕吐哮鸣音,再次给予孟鲁司特钠咀嚼片,咳嗽控制,继续服药,7天后患儿再次用长纸卷塞在耳内,说是耳痛,这次母亲引起了警觉,考虑为孟鲁司特钠引起的不良反应,即停服药物。     

维生素AD滴剂联合孟鲁司特钠治疗毛细支气管炎的疗效观察

目的观察维生素AD滴剂联合孟鲁司特钠咀嚼片治疗毛细支气管炎的临床疗效。方法选择衡水市桃城区妇幼保健院2015年1月—2015年6月确诊的毛细支气管炎患儿80例,随机分为对照组(40例)和治疗组(40例)。对照组口服孟鲁司特钠咀嚼片,6个月以下患儿2 mg/次,6个月以上患儿4 mg/次,每晚1次。治疗组在对照组的基础上加用维生素AD滴剂,1粒/次,1次/d。两组患儿均连续用药7 d。观察两组患儿治疗后的临床疗效和临床症状,比较γ-干扰素(IFN-γ)、免疫球蛋白A(Ig A)、免疫球蛋白G(Ig G)、免疫球蛋白M(Ig M)水平。结果治疗后,对照组和治疗组的总有效率分别为87.5%、95.0%,两组患儿总有效率比较差异具有统计学意义(P0.05)。治疗后治疗组患儿气促、咳嗽、喘憋、肺部体征消失时间和呼吸、心率恢复正常时间与对照组比较差异具有统计学意义(P0.05)。治疗后,两组IFN-γ水平显著升高,同组治疗前后差异有统计学意义(P0.05);且治疗组的上升程度优于对照组,两组比较差异有统计学意义(P0.05)。结论维生素AD滴剂联合孟鲁司特钠治疗毛细支气管炎具有较好的临床疗效,可明显减轻临床症状和体征,不良反应较少,具有一定的临床推广应用价值。     

A simple spectrophotometric method for determination of sodium diclofenac in pharmaceutical formulations

A new, simple, rapid and accurate spectrophotometric method is proposed for determination of sodium diclofenac (SD) in pharmaceutical preparations based on its reaction with concentrated nitric acid (63% w/v). The reaction product is a yellowish compound with maximum absorbance at 380 nm. The corresponding calibration curve is linear over the range of 1-30 mg l(-1), while the limit of detection is 0.46 mg l(-1).     

Pharmacokinetic differences between the enantiomers of lansoprazole and its metabolite, 5-hydroxylansoprazole,in relation to CYP2C19 genotypes

Objective The purpose of this study was to elucidate the pharmacokinetics of each enantiomer of lansoprazole and 5-hydroxylansoprazole in three different CYP2C19 genotype groups of Japanese subjects.Methods Healthy subjects (n=18), of whom 6 were homozygous extensive metabolizers (homEMs), 6 were heterozygous extensive metabolizers (hetEMs) and 6 were poor metabolizers (PMs), participated in the study. After a single oral dose of 60 mg of racemic lansoprazole, the plasma concentrations of the lansoprazole enantiomers, 5-hydroxylansoprazole enantiomers and lansoprazole sulfone were measured for 24 h post-dose.Results The plasma concentrations of (R)-lansoprazole were remarkably higher in all three CYP2C19 genotype groups than those of the corresponding (S)-enantiomer. The mean maximum plasma concentration (C _max) of (S)-lansoprazole differed significantly among the three groups, whereas there was no difference for the (R)-enantiomer. The relative area under the plasma concentration (AUC) ratios of (R)- and (S)-lansoprazole in the homEMs, hetEMs, and PMs were 1:1.5:4.0 and 1:1.8:7.4, respectively. Yet, the relative AUC ratios of 5-hydroxylansoprazole to lansoprazole for the (R)- and (S)-enantiomers in the homEMs, hetEMs, and PMs were almost the same (1:0.73:0.12 and 1:0.77:0.13, respectively). However, the AUC ratios of the (S)-enantiomer were 13-fold greater for the three CYP2C19 genotypes than those of the corresponding (R)-enantiomer.Conclusions The magnitude of the contribution of CYP2C19 to the 5-hydroxylation of (S)-lansoprazole was greater than that of the (R)-enantiomer. The R/S ratios for the AUC of lansoprazole for the homEMs, hetEMs and PMs were 12.7, 8.5 and 5.8, respectively, suggesting a significant effect of CYP2C19 polymorphisms on the stereoselective disposition of lansoprazole.     

头孢唑林钠中间体TDA溶剂化物的工艺改进

对头孢唑林钠中间体TDA溶剂化物的工艺进行改进。将TDA进行真空干燥,提高反应温度,优化盐酸用量,反应过程采用气体保护,收率提高了2％,产品质量得到较大提高。     

测定苯甲酸钠含量的新方法

目的建立用两点电位滴定法直接测定苯甲酸钠含量的方法。方法只需在化学计量点后适当位置测定两组滴定数据,即可确定化学计量点。结果平均偏差0.063,平均回收率为99.61%,RSD=0.21%(n=3)。结论所用方法简便、快速、准确,测定结果与药典法基本一致。     

直接结晶苄青霉素钠的新方法

经超滤处理后的青霉素发酵滤液,按现行工艺所得苄青霉素酸,可直接结晶苄霉素钠盐,改变了由钾盐转钠盐的间接法传统工艺,使钠盐收率提高６．７６％,其２８０ｎｍ吸光值小于０．０４,符合苄青霉素钠钠盐２８０ｎｍ吸光值小于０．０５的药典要求。     

A size-exclusion HPLC method for the determination of sodium chondroitin sulfate in pharmaceutical preparations

A size-exclusion HPLC method for the determination of sodium chondroitin sulfate (SCS) in pharmaceutical preparations has been developed and validated. The most important feature of this method compared with the previously reported assay methods was improved economical and determinative applications through direct analysis of SCS from pharmaceuticals. The linearity, precision, specificity, and accuracy of the method were established and validated. The intra- and inter-day precision was satisfactory with relative standard deviation lower than 1.0%. The recovery of SCS from multi-components pharmaceutical preparations were from 93.38 to 100.46%. Comparing our HPLC assay results with classical spectrophotometric methods, the developed method was considerably easy, simple and reproducible. As a result, the present method was supposed to be successfully applied to the assay of SCS for the routine quality control in pharmaceutical preparations.     

头孢地嗪钠中间体2-巯基-4-甲基-5-噻唑乙酸的合成研究

对头孢地嗪钠的关键中间体2-巯基-4-甲基-5-噻唑乙酸(1)的合成工艺进行了研究，对关键的氯化反应及环合反应进行了适合工业化生产的改进。将乙酰丙酸甲酯与硫酰氯在四氯化碳中于40℃反应6h，得到3-氯乙酰丙酸甲酯(4)，收率84％；4与二硫氨基甲酸铵在50％丙酮-水中于25℃环合反应4h，得到2-巯基-4-甲基-5-噻唑乙酸甲酯(5)，收率81．6％；5在30％氢氧化钠中于25℃水解2．5h，盐酸酸析，得到化合物1，收率94．1％。三步反应总收率64．5％，较文献收率52．7％有较大提高，产品含量≥99．5％(HPLC)，生产成本大幅降低。此合成路线在中试生产中获得成功。     

Relative bioavailability of two disopyramide capsules in humans based on total,unbound, and unbound enantiomer concentrations

The relative bioavailability of two 100-mg disopyramide formulations which showed almost an 8- to 10-fold difference in their dissolution rates at pH 1.2 and 6.8 was determined in eight healthy subjects using a randomized block design. Although no significant differences in relative bioavailability were observed between the two formulations when based on the total disopyramide concentration, an almost 30 per cent difference in the extent of bioavailability was observed when assessed in terms of the unbound (±)- and (?)-disopyramide concentration, due probably to stereoselective nonlinear plasma protein binding. This suggests that unbound enantiomer parameters would be more sensitive to differences in bioavailability between two disopyramide formulations. Therefore, the type of concentration used would be an important factor for precise evaluation of the relative bioavailability of racemic drugs.     

Stability indicating method for sodium montelukast in pharmaceutical preparations by micellar electrokinetic capillary chromatography

A simple, reliable micellar electrokinetic chromatography method (MEKC) for the determination of sodium montelukast in coated tablets was developed and validated. Successful results were obtained with 10 mmol L(-1) borate buffer and 30 mmol L-(1) sodium dodecyl sulfate at pH 9.4, injection time of 5.0 s, an applied voltage of 25 kV and a column temperature of 25 degrees C. The detector response for sodium montelukast was linear over the concentration range from 20 to 100 microg mL(-1) (r = 0.9995). The intra and inter-day precision showed suitable results (RSD < 1.46%). The analytical method accuracy was 99.67% (RSD = 1.11%). The limits of detection and quantitation were 0.75 and 2.00 microg mL(-1) respectively. The method demonstrated robustness and showed to be viable for the sodium montelukast determination in pharmaceutical dosage form.