HPLC法测定甲磺酸多沙唑嗪片剂的含量

目的　用HPLC法测定甲磺酸多沙唑嗪片中甲磺酸多沙唑嗪的含量。方法　以ODS为固定相 ,甲醇 水 冰醋酸 二乙胺(6 5 0∶35 0∶10∶2 )为流动相 ,检测波长为 2 46nm ,流速为 1 0ml·min-1,外标法。结果　测得线性范围为 1 0～ 2 0 0mg·L-1,平均回收率为 99 5 %。结论　本法简便 ,准确 ,可靠     

甲磺酸多沙唑嗪片剂的含量、含量均匀度和溶出度的测定

目的 :建立一种测定甲磺酸多沙唑嗪片剂的HLPC法 ,并用该方法测定甲磺酸多沙唑嗪片剂含量、含量均匀度和溶出度。方法 :色谱柱为DikmaC18(15 0mm× 4 6mm ,5 μm) ,流动相 :甲醇 -醋酸缓冲液 (5 2∶4 8,V/V) ;检测波长 2 5 0nm ;柱温 30℃。结果 :甲磺酸多沙唑嗪对照品溶液的线性方程为A =6 0 72 4c +1 94 1(n =7,r =1 0 0 0 ,线性范围 0 5～ 5 0mg·L-1) ,日内、日间RSD均 <2 % ,检测限为 2 5ng(rSN=3)。甲磺酸多沙唑嗪片剂含量在 10 1%～ 10 4 %之间 ,3批片剂 4 5min平均溶出度在 84 %～87%之间 ,含量均匀度A +1 8S <15。结论 :此法适用于甲磺酸多沙唑嗪片剂含量和溶出度测定     

多沙唑嗪片的HPLC测定

采用Ｌｉｃｈｒｏｓｐｈｅｒ６０ＲＰ－ｓｅｌｅｃｔＢ色谱柱，以ＨＰＬＣ法测定多沙唑嗪片的含量。在１０－４０μｇ／ｍｌ范围内浓度与峰面积有良好性关系。平均回收率为９８．２％，ＲＳＤ为１．０％。     

甲磺酸多沙唑嗪缓释片的研制

目的研制甲磺酸多沙唑嗪缓释片,评价其与参比制剂体外释放行为的相似性。方法以羟丙甲纤维素为骨架材料,以乙基纤维素水分散体为包衣材料,采用湿法制粒技术制备甲磺酸多沙唑嗪缓释片,考察了粘合剂种类、包衣处方、包衣增重等对药物释放的影响,并进行了处方工艺验证,对中试放大产品进行体外释放度研究并与参比制剂"可多华"进行对比。结果本品与参比制剂具有相同的释放曲线。结论该制剂处方合理,制备方法可行、工艺稳定、简单、重复性好、成本低、生产效率高、缓释效果良好。     

甲磺酸多沙唑嗪合成路线图解

甲磺酸多沙唑嗪(doxazosinmesylate,Carduran,UK-33274,1),化学名为1-(4-氨基-6,7-二甲氧基-2-喹唑啉基)-4-[(2,3-二氢-1,4-苯并二烷-2-基)羰基]哌嗪甲磺酸盐,由辉瑞公司开发,于1988年在丹麦首次上市。本品为第二代选择性α1受体阻滞剂,具有降压作用强、半衰期长、给药?..     

甲磺酸多沙唑嗪质量标准提高的研究

目的: 提高甲磺酸多沙唑嗪的质量标准。方法: 根据生产厂家提供的工艺等资料,按照《中国药典》2010年版二部的相关规定,参考各厂家注册标准及相关文献,考察本品的紫外鉴别、酸度、干燥失重、有关物质、含量测定等项目。结果: 应修订有关物质检测方法,提高杂质限度要求以及修订含量测定方法。结论：提高后的质量标准能更好地控制甲磺酸多沙唑嗪的产品质量,与国际水平接轨。     

健康志愿者单次口服甲磺酸多沙唑嗪片耐受性研究

目的：在健康志愿受试者中评价单次口服国产甲磺酸多沙唑嗪的安全性和耐受性。方法：选择20名20-40岁健康受试者,随机分配至A（1mg)、B（2mg)、C（4mg)、D（6mg)、E（8mg)剂量组,观察临床症状体征和实验室检查变化。结果：各组入选受试者耐受性较好,4mg以上受试者于服药后1-3h出现轻微鼻塞、头晕,6mg以上受试者出现了直立位低血压。结论：建议首次服用剂量为0.5-1mg,临睡前服用,Ⅱ期临床推荐剂量为每次2mg比较安全,可以耐受。     

甲磺酸伊马替尼片处方工艺研究

目的：研究甲磺酸伊马替尼片的处方工艺。方法：以制剂的溶出曲线为指标,筛选甲磺酸伊马替尼片处方和制备工艺。结果：建立了以微晶纤维素、交联聚维酮和硬脂酸镁为辅料的处方及采用95%乙醇湿法制粒的工艺,制备的3批产品的有关物质、溶出度等指标与参比制剂具有相似性,制剂特性满足制剂质量一致性的要求。结论：甲磺酸伊马替尼片处方合理,工艺简单,易于工业化生产。     

甲磺酸多沙唑嗪缓释片Beagle犬体内药动学和生物等效性研究

目的 研究甲磺酸多沙唑嗪（Dox）缓释片在Beagle犬体内的药动学，评价其生物等效性。方法 8条健康Beagle犬，采用双周期、双交叉、单剂量分别ig Dox缓释片受试制剂或参比制剂4 mg；建立血浆中Dox液相色谱-质谱联用（LC-MS/MS）检测方法，进行方法精密度、准确度、回收率、基质效应、稳定性方法学验证；测定给药前（0 h）及给药后2、3、4、5、6、8、10、12、14、16、24、36、48、72 h血浆中Dox经时血药浓度，运用DAS3.2.8计算其药动学参数，并评价其生物等效性。结果 LC-MS/MS方法学经验证符合检测要求。主要药动学参数如下：受试制剂与参比制剂的C_max分别为（29.998 ±3.725）、（31.207 ±5.586） ng/mL，T_max分别为（11.5 ±2.33）、（11.25 ±1.035） h，AUC_0-t分别为（528.549 ±84.526）、（539.852±94.232） ng· h/mL；受试制剂AUC_0-t、AUC_0-∞和C_max的90%置信区间分别为参比制剂相应参数的84.6%~113.9%、88.6%~107.5%和90.2%~104%，均在80%~125%范围内。结论 Dox缓释片受试制剂与参比制剂生物等效。     

Polymorphism of doxazosin mesylate

Nine polymorphic modifications of doxazosin mesylate have been obtained by recrystallization in organic solvents under variable conditions. Different polymorphs of doxazosin mesylate were characterized by powder X-ray crystallography diffractometry (PXRD), differential scanning calorimetry (DSC), and thermogravimetric analysis (TG). Transformation of Form 1 and Form 2 was not occurred in three relative humidities (0%, 51%, and 99%) at 20 +/- 0.5 for 30 days.     

LC-MS determination and relative bioavailability of doxazosin mesylate tablets in healthy Chinese male volunteers

This study aims to develop a standard protocol for the relative bioavailability testing of doxazosin mesylate tablets. For this purpose, a simple rapid and selective LC-MS method using a single quadrupole mass spectrometer was developed and validated to determine the concentration of doxazosin mesylate in human plasma. Using this method, we carried out a study of relative bioavailability. N-Hexylane-tertiary butyl methyl ether (1:1, v/v) was used to extract doxazosin mesylate and terazosin (internal standard, I.S.) from an alkaline plasma sample. LC separation was performed on a Thermo Hypersil-Hypurity C18 (5 microm, 150 mm x 2.1mm) using aqueous solution (20 mmol/l ammonium acetate, pH 4.28), methanol and acetonitrile (55:10:35, v/v/v) as the mobile phase. The retention time of doxazosin and the internal standard was 2.7 and 1.8 min, respectively. Quadrupole MS detection was done by monitoring at m/z 388 (M+1) corresponding to doxazosin mesylate and at m/z 452 (M+1) for I.S. The assay method described above showed acceptable precision, accuracy, linearity, stability, and specificity. The bioavailability of doxazosin mesylate was evaluated in 12 healthy Chinese male volunteers. The following pharmacokinetic parameters were elucidated after administering a single dose of 4 mg doxazosin. The area under the plasma concentration versus time curve from time 0 to 72 h (AUC(0-72 h)) 743.4+/-149.5 ngh/ml; peak plasma concentration (C(max)) 47.66 ng/ml; time to C(max) (T(max)) 3.0+/-1.0 h; and elimination half-life (t(1/2)) 18-20 h. The method was successfully used to determine the relative bioavailability of doxazosin mesylate.     

Flow injection analysis of doxazosin mesylate using UV-detection

A flow injection analysis (FIA) of doxazosin mesylate (DOX) using UV detection is described in this study. The best solvent system was found to be consisting of 0.1 mol l(-1) acetate buffer at pH 4 having 10%MeOH. A flow rate of 1 ml min(-1) was pumped and active material was detected at 365 nm. The calibration equation was linear in the range of 1.3 x 10(-5) to 6.4 x 10(-5) mol l(-1). Limit of detection and limit of quantitation were calculated to be 1.6 x 10(-6) and 4 x 10(-6) mol l(-1) with a RSD 1.27 and 1.16% (n=8), respectively. The proposed method was applied to the determination of DOX in the pharmaceutical preparations. The results were compared with those obtained from UV-Spectrophotometry. The results showed that there is a good agreement between FIA method and UV-Spectrophotometry. The validation studies were realised by the related applications and the results were evaluated statistically. According to the results, insignificant difference was observed between the methods.     

甲磺酸酚妥拉明泡腾片的处方及制备工艺研究

目的:利用普通制剂技术制备起效快、服用方便的甲磺酸酚妥拉明泡腾片。方法:通过实验优化筛选甲磺酸酚妥拉明泡腾片的辅料及其配比,并对制剂进行初步的质量评价。结果:优化处方的甲磺酸酚妥拉明泡腾片的崩解时限、片重差异、硬度等指标均符合或优于中国药典2005版附录的相关要求。结论:本品处方和制备方法有效可行,可作为甲磺酸酚妥拉明的一种新剂型开发。     

多沙唑嗪控释片对血脂影响的实验研究

多沙唑嗪为降血压药物,近年发现有降血脂作用.为此,本文对其进行了实验研究. 1材料与方法 1.1动物模型 新西兰兔,23只,年龄：110～130天,♂♀不限,体质量：2.0～2.5 kg,由昆明医学院动物科提供.试验前,适应性饲养2周,排除饮食异常者,稳定血脂水平和代谢状况.     

多沙唑嗪治疗原发性高血压38例疗效观察

目的 观察多沙唑嗪治疗原发性高血压的临床疗效.方法 38例Ⅰ或Ⅱ期原发性高血压患者服用多沙唑嗪控释片4～8 mg/d,4周,观察治疗前后诊所血压(CBP)、超声心动图及生化指标的变化.结果 多沙唑嗪治疗后血压下降明显,总有效率87%,对血糖、血脂和心功能无不良影响.结论 多沙唑嗪是治疗高血压的有效药物,安全、耐受性好.