盐酸氨溴索注射液降解杂质结构与降解途径分析

目的：对盐酸氨溴索注射液在氧化和光照条件下强制破坏产生降解杂质的结构和来源进行研究。方法：通过对盐酸氨溴索注射液在各条件下进行强制破坏,产生降解杂质,采用VisionHT C18色谱柱（250 mm × 4.6 mm,5 μm）。以0.01 mol·L-1磷酸氢二铵溶液（用磷酸调节pH至7.0）-乙腈（50∶50）洗脱,分离制备有关物质,采用质谱法,对主要降解产物的结构进行研究。归属杂质来源,推测形成路径。结果：确定了盐酸氨溴索注射液中8个降解杂质的分子结构,并明确了其质谱裂解反应机理。结论：成功推测了盐酸氨溴索注射液强制氧化和光降解产物的结构,并阐明其产生的路径。     

盐酸氨溴索注射液配伍稳定性文献分析

目的根据临床应用过程中盐酸氨溴索注射液与各种常用药物联合应用引起的配伍禁忌的文献报告,分析氨溴索注射液的配伍稳定性。方法通过中国医院知识仓库(简称CHKD)收集1994~2011年临床资料,进行总汇、分析。结果检索得到54篇有关氨溴索注射液配伍文献报道,有关配伍药物共47个药品。盐酸氨溴索注射液与部分常用抗感染药(主要为头孢类)、中药注射液、甲强龙、奥美拉唑、泮托拉唑、呋塞米注射液等药品伍用,均会引起变色、沉淀等现象,提示临床应用中存在配伍禁忌,与各种大输液、果糖、氯化钾注射液、克林霉素磷酸酯、加替沙星注射液、维生素B6等药品伍用,性状含量稳定,宜配伍。结论盐酸氨溴索注射液经常与各种药物同时使用,已经明确存在配伍禁忌的应避免在同一瓶输液中配伍。     

盐酸氨溴索杂质B对照品溶液稳定性的研究

目的:对盐酸氨溴索杂质B在不同溶剂中的稳定性进行研究.方法:将盐酸氨溴索杂质B分别溶解于流动相[pH 7.0磷酸盐缓冲液-乙腈(50:50)]、水、乙腈-水(50:50)和甲醇中,采用HPLC法测定,考察其色谱纯度随时间变化情况,利用HPLC以及LC-MS对降解产物进行结构鉴定,并从化学反应机理上分析降解过程以及不同溶...     

盐酸艾司洛尔注射液中杂质的分离、合成与结构鉴定

目的:研究盐酸艾司洛尔注射液中杂质的结构和产生的原因。方法:采用制备高效液相色谱方法制备分离盐酸艾司洛尔注射液的杂质并采用IR、MS1、H-NMR、13C-NMR等方法进行结构鉴定;合成制备了此杂质并进行结构确证。结果:该杂质为4-{[2-羟基-3-[(1-甲基乙基)氨基]]丙氧基}苯丙酸盐酸盐,为盐酸艾司洛尔注射液在储藏过程的降解产物。结论:本研究可为盐酸艾司洛尔注射液质量评价提供依据。     

盐酸氨溴索注射液在果糖注射液中的配伍稳定性研究

目的考察25℃和37℃下盐酸氨溴索注射液在果糖注射液中配伍的稳定性。方法采用高效液相色谱法测定氨溴索与果糖注射液配伍一定时间后的含量,同时观察外观变化并测定其pH值。结果药物在25℃和37℃果糖注射液中配伍后,0-8 h内其外观、pH值及含量均无明显变化。结论两药液配伍后在8 h内稳定,可配伍使用。     

HPLC 法测定盐酸氨溴索注射液中有关物质

目的采用HPLC法测定盐酸氨溴索注射液中的有关物质。方法采用Agela Venusil MPC18柱(250mm×4.6mm,5μm),以磷酸氢二铵缓冲液(pH4.0)-甲醇(40:60)为流动相,体积流量为1.0mL/min,检测波长为250nm,柱温:30℃。结果盐酸氨溴索和反式-4-[6,8-二溴-1,4-二氢喹唑啉-3(2H)]环己醇的最小检出限分别为15、30ng;杂质的线性范围为0.72～1.68μg/mL(r=0.9996),加样平均回收率为101.32%,RSD为0.92%(n=9)。结论该方法测定盐酸氨溴索注射液中的有关物质方法简便、准确、专属性强。     

注射用盐酸川芎嗪的配伍稳定性考察

目的考察注射用盐酸川芎嗪溶液的稳定性。方法测定溶液的pH值。采用HPLC法测定溶液中注射用盐酸川芎嗪的含量,定时观察溶液的颜色及澄明度。观察注射用盐酸川芎嗪在常用输液5％葡萄糖注射液（5％GS）、10％葡萄糖注射液（10％GS）、0．9％氯化钠注射液（0．9％NS）、葡萄糖氯化钠注射液（GNs）、10％果糖注射液中的稳定性。结果注射用盐酸川芎嗪与果糖等常用输液配伍后．各项结果在8h内均无明显变化。结论注射用盐酸川芎嗪可与果糖等常用输液配伍使用。     

注射用盐酸川芎嗪的配伍稳定性考察

目的考察注射用盐酸川芎嗪溶液的稳定性。方法测定溶液的pH值,采用HPLC法洲定溶液中注射用盐酸川芎嗪的含量,定时观察溶液的颜色及澄明度。观察注射用盐酸川芎嗪在常用输液5％葡萄糖注射液（5％GS）、10％葡萄糖注射液（10％GS）、0．9％氧化钠注射液（0．9％NS）、葡萄糖氯化钠注射液（GNS）、10％果糖注射液中的稳定性。结果注射用盐酸川芎嗪与果糖等常用输液配伍后,各项结果在8h内均无明显变化。结论注射用盐酸川芎嗪可与果糖等常用输液配伍使用。     

沐舒坦注射液在3种常用输液中的稳定性

目的:比较沐舒坦注射液在5%葡萄糖注射液,0.9%氯化钠注射液,乳酸林格氏注射液中的稳定性.方法:在沐舒坦注射液加入输液6 h内,采用HPLC法测定盐酸氨溴索的含量,采用pH计测定输液pH值,并肉眼观察输液的颜色和澄明度.结果:在沐舒坦注射液加入输液6 h内,盐酸氨溴索的含量和pH值均保持稳定,输液的颜色和澄明度也未发生变化.结论:沐舒坦注射液的在3种常用输液中是稳定的.     

注射用头孢替安与盐酸氨溴索注射液的配伍稳定性考察

目的:考察室温下注射用盐酸头孢替安与盐酸氨溴索注射液在0.9%氯化钠注射液中的配伍稳定性。方法:采用反相高效液相色谱法-二极管阵列检测器测定配伍液0～8h头孢替安与盐酸氨溴索的含量,同时测定pH值,并观察配伍液的外观变化。结果:在室温((20±1)℃)下、8h内,配伍液外观、pH值及含量均变化明显。结论:在室温((20±1)℃)下,在盐酸头孢替安与盐酸氨溴索注射液不宜在0.9%氯化钠注射液中配伍使用。     

盐酸氨溴索葡萄糖注射液致过敏性休克

1例75岁男性患者因肺部感染给予静脉滴注盐酸氨溴索葡萄糖注射液50 ml(含盐酸氨溴索30 mg及葡萄糖2.5 g)。约30 min后,患者突发胸闷、冷汗、恶心、头晕。体格检查:血压40/0 mm Hg(1 mmHg=0.133 kPa),口唇发绀,面色苍白,四肢冷,意识模糊。立即停止静脉滴注,行心电监护,并给予吸氧及地塞米松、异丙嗪、多巴胺等药物治疗。4 h后患者血压平稳,130/70 mm Hg,其余生命体征正常,症状消失。住院2周期间,未再静脉滴注盐酸氨溴索葡萄糖注射液,未再发生类似反应。     

盐酸氨溴索静脉用药协同雾化吸入治疗29例老年呼吸系统感染性疾病疗效观察

目的：观察盐酸氨溴索雾化吸入治疗老年呼吸系统感染性疾病的效果。方法：收集2014年7月－2015年6月年龄＞80岁的老年呼吸系统感染性疾病患者58例,随机分为治疗组29例,静脉滴注盐酸氨溴索60 mg,每天1次,同时雾化吸入盐酸氨溴索15 mg,每天2次,每次15 min;对照组29例,静脉滴注盐酸氨溴索60 mg,每天1次。两组均给予常规抗生素和解痉平喘治疗,观察两组治疗效果。结果：治疗组总有效率为86.21%（25/29）,显著高于对照组的75.86%（22/29,P＜0.05）。临床体征咳嗽、咳痰好转或终止时间短于对照组,肺部啰音消失时间快于对照组,抗生素使用时间短于对照组。结论：盐酸氨溴索静脉用药协同雾化吸入治疗老年呼吸系统感染性疾病起效快,且安全,值得临床推广。     

Determination of ambroxol in human plasma using LC-MS/MS

A sensitive and selective liquid chromatographic method coupled with tandem mass spectrometry (LC-MS/MS) was developed for the quantification of ambroxol in human plasma. Domperidone was used as internal standard, with plasma samples extracted using diethyl ether under basic condition. A centrifuged upper layer was then evaporated and reconstituted with 200 microl methanol. The reconstituted samples were injected into a C(18) XTerra MS column (2.1 x 30 mm) with 3.5 microm particle size. The analytical column lasted for at least 600 injections. The mobile phase was composed of 20 mM ammonium acetate in 90% acetonitrile (pH 8.8), with flow rate at 250 microl/min. The mass spectrometer was operated in positive ion mode using turbo electrospray ionization. Nitrogen was used as the nebulizer, curtain, collision, and auxiliary gases. Using MS/MS with multiple reaction monitoring (MRM) mode, ambroxol was detected without severe interferences from plasma matrix. Ambroxol produced a protonated precursor ion ([M+H](+)) at m/z 379 and a corresponding product ion at m/z 264. And internal standard (domperidone) produced a protonated precursor ion ([M+H](+)) at m/z 426 and a corresponding product ion at m/z 174. Detection of ambroxol in human plasma was accurate and precise, with quantification limit at 0.2 ng/ml. This method has been successfully applied to a study of ambroxol in human specimens.     

Degradation profile and identification of the major degradation products of dobupride under several conditions by GC/MS and HPLC-particle beam/MS

The effect of pH, light, temperature and oxygen on the stability of dobupride (1), a novel gastroprokinetic drug, has been studied, storing the sample in the solid state and as a solution in methanol-water. The main forced degradation products have been identified by means of techniques such as GC/MS and HPLC-particle beam/MS, and two major degradation pathways have been characterized. One degradation route involves the loss of chlorine, yielding 4-amino-2-butoxy-N-[1-(1,3-dioxolan-2-ylmethyl)piperid-4-yl]benzamide (4) as the major degradation product. The second pathway results from cleavage of the piperidine-amide bond, producing 4-amino-2-butoxy-5-chlorobenzamide (2) as the major degradation product. Under the studied conditions, except when exposed to direct light in solution, dobupride has been shown to be very stable: after 5 months storage, the benzamide 2 (second pathway) was the only product identified (less than 0.5%). However, when dobupride in solution is exposed to natural or artificial sunlight, degradation is very fast, and after 7 days only 5% of the unchanged product remains. Under these circumstances, the main degradation route is the first one, with compound 4 being the most abundant degradation product, and compound 2 only being detectable in small amounts.     

沐舒坦佐治新生儿肺炎疗效观察

目的探讨沫舒坦不同给药途径治疗新生儿肺炎的疗效。方法将2007年1月-2008年12月我科确诊为新生儿肺炎180例,随机分成4组,其中对照组采用吸氧,青霉素或头抱三嗪抗感染,补液等常规处理;（静脉静滴）治疗组1在对照组基础上加用沐舒坦静滴;（雾化）治疗组2在对照组基础上加用沐舒坦用氧气作驱动力雾化吸入;（静脉静滴＋雾化）治疗组3在对照组基础上加用沐舒坦静滴及沐舒坦用氧气作驱动力雾化吸入。结果治疗组在临床症状、体征及住院日均短于对照组（P〈0．01及P〈0．05）,治疗组疗效优干对照组,差异有统计学意义。结论沐舒坦无论是静脉滴注还是雾化吸入治疗新生儿肺炎具有疗效显著．安全．基层医院可以应用。     

大剂量盐酸氨溴索防治新生儿呼吸窘迫综合征的疗效观察

目的探讨盐酸氨溴索对新生儿呼吸窘迫综合征（NRDS）的预防和治疗效果。方法对照组32例早产儿给予常规综合治疗;治疗组33例早产儿在常规综合治疗的基础上,加用盐酸氨溴索,7．5mg·kg^-1,静脉注射,每6h1次,疗程共5d。结果治疗组NRDS的发生率为18．18％,对照组NRDS的发生率为34．38％,有显著差异性（P〈0．05）;治疗组和对照组平均住院时间分别为（13．56±3．18）d、（15．32±2．92）d,平均住院费用分别为（5870±672．5）元、（6356±723．7）元,有显著差异性（P〈0．05）。结论大剂量盐酸氨溴索对NRDS有一定的预防和治疗作用,值得临床推广应用。     

Inhalation of ambroxol inhibits cigarette smoke-induced acute lung injury in a mouse model by inhibiting the Erk pathway

Oral and injection administration of ambroxol has been clinically used to treat airway disease. However, little is known about its potentials in inhalation therapy. In present studies, we tested the effects of ambroxol by inhalation with intravenous administration, and explored the underlying working mechanism. The mice received 10 cigarettes exposure every day for 4 days. Inhaled solution of ambroxol was aerosolized 20 min before the exposure of cigarette smoke (CS). The effect of ambroxol on the expression of mucoprotein 5AC (MUC5AC) and proinflammatory cytokines in NCI-H292 cells stimulated with cigarette smoke extract (CSE). Four days of daily inhalation of ambroxol at 3.75 or 7.5 mg/ml for 20 min suppressed the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) and lung tissues, and inhibited increases in the mRNA and protein levels of tumor necrosis factor (TNF)-α, CCL-2 and KC, but not interleukin (IL)-1β in the CS-exposed mice. Moreover, ambroxol at 3.75 or 7.5 mg/ml facilitated airway mucosa cilia clearance, reduced glycosaminoglycans level in BALF and MUC5AC mRNA levels in lung tissues. The effects of ambroxol by inhalation at 7.5 mg/ml was comparable to that of ambroxol at 20 mg/kg i.v. and dexamethasone at 0.5 mg/kg i.p. Using cultured lung epithelial cells, we demonstrated that pretreatment with ambroxol at 2 or 20 μM inhibited the CSE-induced up-regulation of MUC5AC, TNF-α, IL-1β mRNA levels, which was through inhibiting Erk signaling pathway. Our results demonstrate the beneficial effects of ambroxol as an inhalation replace systemic administration for COPD therapy.     

盐酸氨溴索注射剂与常用抗生素的配伍稳定性

目的检测室温(20℃)和冰箱温度(4-10℃)下盐酸氨溴索注射剂与临床常用5种抗生素的配伍稳定性。方法用HPLC法测定5种配伍液在不同配伍时间的盐酸氨溴索含量变化及pH值。结果盐酸氨溴索注射液与5种抗生素配伍,室温6 h内,配伍液的pH值和盐酸氨溴索含量无明显变化;冰箱温度24 h内,与头孢唑林钠的配伍液,随时间延长pH值逐渐升高,溶液逐渐浑浊,h 12盐酸氨溴索含量降至59．88％。结论室温6 h内,盐酸氨溴索注射液与注射用青霉素钾、乳糖酸红霉素、头孢曲松钠、头孢哌酮钠、头孢唑林钠配伍稳定;冰箱温度24 h内,与头孢唑林钠配伍不稳定。     

LC-MS法分析拉米夫定的有关物质

目的建立检测拉米夫定中有关物质的液质联用分析方法,分析鉴定拉米夫定原料药、加速破坏样品和制剂产品中的有关物质,并推测其可能的降解途径。方法色谱柱为Syncronjs C_(18)柱,以5 mmol·L^(-1)乙酸铵-甲醇为流动相,线性梯度洗脱,对拉米夫定有关物质进行分离。分别在正负离子模式下采用一级全扫描和自动二级全扫描方式对样品进行质谱检测。结果拉米夫定及其各有关物质分离良好,共检测到13种有关物质。结果表明,拉米夫定的主要降解反应为氧化、差向异构化、脱氨和水解。在酸性和高温条件下,药物的稳定性良好,但在碱性和氧化条件下,药物稳定性较差。制剂产品中有关物质的种类较原料药有显著增加。结论该方法适用于拉米夫定有关物质和降解途径的研究,试验中检测到的有关物质,推测的降解途径及该类物质的质谱行为规律为该产品的质量控制及稳定性研究提供了重要的依据。