高效液相色谱法测定复方氨酚美沙糖浆中盐酸甲基麻黄碱、愈创甘油醚、氢溴酸右美沙芬的含量

目的建立复方氨酚美沙糖浆中盐酸甲基麻黄碱、愈创甘油醚、氢溴酸右美沙芬的定量分析方法。方法采用HPLC法测定,色谱柱为Agilent HC-C18（4.6 mm×250 mm,5μm）;流动相为甲醇—0.1%磷酸,梯度洗脱;流速为1 mL·min^-1,检测波长为216 nm。结果盐酸甲基麻黄碱、愈创甘油醚、氢溴酸右美沙芬分别在0.141 2-1.412、0.605-6.05、0.156 8-1.568μg范围内线性关系良好（r分别为0.999 6、0.999 8、0.999 5）;平均回收率分别为100.05%、98.69%、99.68%,RSD分别为2.24%、1.85%、2.03%（n=9）。结论该法快速准确,重复性好,可为复方氨酚美沙糖浆的质量控制提供定量评价方法。     

愈创维林那敏胶囊三组分的反相高效液相色谱法同时快速测定

目的:建立能够同时快速测定愈创维林那敏胶囊三组分的 RP-HPLC 法。方法:采用 Inertsil C_(18)色谱柱(150 mm×4.6mm,5 μm),以0.5%磷酸溶液(含0.5%三乙胺,氨水调 pH 为5.5)-乙腈(66:34)为流动相,流速为1.0 mL·min~(-1),检测波长为250 nm,柱温为室温。采用外标法计算含量。结果:在一定浓度范围内,愈创甘油醚、枸橼酸喷托维林、马来酸氯苯那敏峰面积与浓度均呈良好的线性关系(r>0.9990)。平均回收率(n=9)分别为100.0%,99.8%,99.6%。结论:该法简便、快速、准确,可用于该制剂的质量控制。     

两种口服液治疗儿童急性支气管炎的疗效对比

目的对比分析愈酚伪麻与盐酸氨溴索口服溶液治疗儿童急性支气管炎的疗效。方法选取我院收治的297例急性支气管炎患儿随机分成实验组(148例)与对照组(149例)。实验组口服愈酚伪麻溶液,对照组口服盐酸氨溴索溶液,所有患儿的疗程均为1周。对比分析两组的疗效及不良反应。结果治疗3 d,7 d后,实验组各项症状与综合积分与白细胞数明显优于对照组(P<0.05);治疗7 d后,实验组的疗效要显著优于对照组(P<0.05);两组发生不良反应情况的差异比较无统计学意义(P>0.05)。结论愈酚伪麻口服溶液治疗儿童急性支气管炎较盐酸氨溴索口服溶液能更快地改善患儿的临床症状,且不良反应较少。     

HPLC法测定复方愈酚麻黄糖浆中愈创甘油醚和马来酸氯苯那敏

目的：建立测定复方愈酚麻黄糖浆中愈创甘油醚和马来酸氯苯那敏含量的高效液相色谱法（HPLC）。方法: 色谱柱为Agilent SB-C18柱（4.6mm×250 mm,5?m）,流动相：乙腈- 0.02 mol?L-1磷酸二氢钾（含0.1%三乙胺,用磷酸pH至3.0）（25:75）,检测波长：260nm,流速1.0mL?min-1,柱温：25℃。结果：愈创甘油醚在0.0120～1.2035?g范围内线性关系良好,回归方程Y=296882X+31351（R2=0.9998）,方法回收率在99.50～ 102.82%之间（RSD在0.06～0.41%之间）（n=9）,13批样品的愈创甘油醚含量在98.23～102.84%之间;马来酸氯苯那敏在0.0061～0.6055?g范围内线性关系良好,回归方程Y=752335x-921.9（R2=1.0000）,方法回收率在97.70～ 98.46%之间（RSD在0.32～0.64%之间）（n=9）,13批样品的马来酸氯苯那敏含量在92.39～101.22%之间;结论：该方法简便,快速,准确,可用于该制剂中愈创甘油醚和马来酸氯苯那敏的含量测定。     

愈创木酚甘油醚缓释片不同湿度下颗粒的流动性变化与片剂质量间的关系

 目的 考察环境湿度对愈创木酚甘油醚缓释片颗粒流动性的影响,探求颗粒流动性变化和片剂质量之间的关系,为该品种的工业化生产提供依据。方法 对颗粒的吸湿性进行初步研究,求取颗粒的临界相对湿度（CRH）。 以0 d的颗粒和片剂为参比,考察颗粒暴露在RH 33%、60%、75%、84%、92.5%下10 d后流动性的变化,测量相应颗粒制得的片剂的质量指标,探讨颗粒流动性变化与片剂质量之间的关系。结果 颗粒的CRH在RH 67%~68%之间。在湿度高于RH 60%下10 d后,颗粒流动性、水分含量、片剂的外观、片重差异极值、脆碎度都有明显改变。以颗粒的压缩度（X1）、休止角（X2）为自变量,片重差异极值（Y1）、脆碎度（Y2）为因变量进行二元回归分析得：Y1=0.192X1+0.092X2-7.398（r=0.992 1）,Y2=0.069X1+0.087X2-3.505（r=0.988 1）,P<0.001时,在观测范围内具有统计学意义。结论 颗粒的生产和储存的环境湿度应小于RH 60%,颗粒的休止角和压缩度与片剂的质量指标（片重差异极值、脆碎度）间存在统计学意义上的函数关系。
     

Bitterless guaifenesin prodrugs—design,synthesis, characterization,in vitro kinetics,and bitterness studies

A respected number of drugs suffer from bitter taste which results in patient incompliance. With the aim of solving the bitterness of guaifenesin, dimethyl maleate, maleate, glutarate, succinate, and dimethyl succinate prodrugs were designed and synthesized. Molecular orbital methods were utilized for the design of the ester prodrugs. The density functional theory (DFT) calculations revealed that the hydrolysis efficiency of the synthesized prodrugs is significantly sensitive to the pattern of substitution on C=C bond and distance between the nucleophile and the electrophile. The hydrolysis of the prodrugs was largely affected by the pH of the medium. The experimental t_1/2 for the hydrolysis of guaifenesin dimaleate ester prodrugs in 1N HCl was the least and for guaifenesin dimethyl succinate was the highest. Functional heterologous expression of TAS2R14, a broadly tuned bitter taste receptor responding to guaifenesin, and experiments using these prodrugs revealed that, while some of the prodrugs still activated the receptor similarly or even stronger than the parent substance, succinate derivatization resulted in the complete loss of receptor responses. The predicted binding modes of guaifenesin and its prodrugs to the TAS2R14 homology model suggest that the decreased activity of the succinate derivatives may be caused by a clash with Phe247.     

愈美分散片人体药动学及制剂生物等效性研究

建立了同时测定人血浆中氧去甲右美沙芬及愈创木酚甘油醚浓度的高效液相色谱 紫外检测法 ,并初步研究了以上两种药物在人体内的药动学性质。运用此法对 18名健康男性受试者单剂量交叉口服愈美分散片 (受试制剂 )和速立糖浆 (参比制剂 )后的酶水解血浆进行测定 ,并绘制了血浆药物浓度 时间曲线。口服愈美分散片测得 :氧去甲右美沙芬Tmax为 (1 89± 0 5 3)h ,Cmax为 (892 6±315 0 )ng/mL ,AUC0 -t为 (4 15 3 2± 115 1 9)ng·h·mL-1;愈创木酚甘油醚Tmax为 (0 6 5± 0 2 7)h ,Cmax为 (15 45 1± 493 6 )ng/mL ,AUC0 -t为 (2 6 89 8± 72 8 2 )ng·h·mL-1。口服速立糖浆测得 :氧去甲右美沙芬Tmax为 (1 81± 0 2 5 )h ,Cmax为 (85 5 0± 2 0 7 6 )ng/mL ,AUC0 -t为 (4 0 0 1 8± 75 3 5 )ng·h·mL-1;愈创木酚甘油醚Tmax 为 (0 5 0± 0 2 1)h ,Cmax 为 (1942 4± 437 6 )ng/mL ,AUC0 -t为 (3382 8±85 6 5 )ng·h·mL-1。氧去甲右美沙芬的相对生物利用度平均为 (10 3 6± 19 3) % ,愈创木酚甘油醚的相对生物利用度平均为 (86 9± 13 4) %。统计结果表明 ,两种制剂生物等效     

复方抗感冒药中三组分的反相离子对HPLC测定

研究了双通道反相离子对ＨＰＬＣ法同时测定复方抗感冒药中盐酸伪麻黄碱、氢溴酸右美沙芬和愈创木酚甘油醚含量的实验条件。三组分的平均回收率分别为９９．１±０．８５％、１００．７±１．０２％和１００．８±１．９８％。     

愈美干混悬剂在健康志愿者体内的生物等效性研究

目的：建立高效液相色谱-荧光法（HPLC-FD）测定血浆中氧去甲右美沙芬1和愈创木酚甘油醚2的血药浓度,并研究愈美干混悬剂的相对生物利用度及生物等效性。方法：20名健康志愿者分两组,随机、交叉口服单剂量愈美干混悬剂（受试制剂）和愈美片（参比制剂）,HPLC法测定血药浓度,计算药代动力学参数及生物等效性评价。结果：受试制剂与参比制剂血浆中氧去甲右美沙芬的T1/2：（4.13±0.87）h和（3.48±1.18）h;Cmax：（1 136.79±242.38）ng/ml和（1 069.79±237.26）ng/ml;Tmax：（1.65±0.33）h和（2.08±0.44）h;AUC0-t：（5 893.07±938.43）ng.h/ml和（5 601.46±873.04）ng.h/ml;愈创木酚甘油醚的T1/2：（0.88±0.10）h和（0.86±0.23）h;Cmax：（1 495.27±319.32）ng/ml和（1 432.73±296.47）ng/ml;Tmax：（0.61±0.13）h和（0.71±0.12）h;AUC0-t：（2 091.43±413.87）ng.h/ml和（2 056.16±424.27）ng.h/ml。愈美干混悬剂的相对生物利用度氧去甲右美沙芬为（105.60±9.90）%,愈创木酚甘油醚为（102.10±6.80）%。结论：两制剂生物等效。     

Stability-indicating HPLC Method for Simultaneous Determination of Terbutaline Sulphate, Bromhexine Hydrochloride and Guaifenesin

The aim of the present study was the development and subsequent validation of a simple, precise and stability-indicating reversed phase HPLC method for the simultaneous determination of guaifenesin, terbutaline sulphate and bromhexine hydrochloride in the presence of their potential impurities in a single run. The photolytic as well as hydrolytic impurities were detected as 3,5-dihydroxybenzoic acid, 3,5-dihydroxybenzaldehyde, 1-(3,5-dihydroxyphenyl)-2-[(1,1-dimethylethyl) amino]-ethanone from terbutaline, 2-methoxyphenol and an unknown impurity identified as (2RS)-3-(2-hydroxyphenoxy)-propane-1,2-diol from guaifenesin. The chromatographic separation of all the three active components and their impurities was achieved on Wakosil II column, using phosphate buffer (pH 3.0) and acetonitrile as mobile phase which was delivered initially in the ratio of 80:20 (v/v) for 18 min, then changed to 60:40 (v/v) for next 12 min, and finally equilibrated back to 80:20 (v/v) for 10 min. Other HPLC parameters were: Flow rate at 1.0 ml/min, detection wavelengths 248 and 280 nm, injection volume 10 μl. The calibration graphs plotted with five concentrations of each component were linear with a regression coefficient R(2) >0.9999. The limit of detection and limit of quantitation were estimated for all the five impurities. The established method was then validated for linearity, precision, accuracy, and specificity and demonstrated to be applicable to the determination of the active ingredients in commercial and model cough syrup. No interference from the formulation excipients was observed. These results suggest that this LC method can be used for the determination of multiple active ingredients and their impurities in a cough and cold syrup.