复方厄贝沙坦片中厄贝沙坦和氢氯噻嗪的HPLC测定

建立同时测定复方厄贝沙坦片中厄贝沙坦和氢氯噻嗪含量的HPLC方法。用Inertsil ODS-3色谱柱，流动相为乙腈-0．08mol／L磷酸溶液(用三乙胺调至pH5．0)(40：60)，检测波长225nm。厄贝沙坦和氢氯噻嗪分别在15～135μg／ml(r=0．9999)和1．2～10．8μg／ml(r=0．9999)浓度范围内线性关系良好，方法平均回收率分别为100．0％(RSD=0．46％)和100．5％(RSD=0．49％)。     

厄贝沙坦氢氯噻嗪治疗轻中度高血压的疗效观察

目的观察厄贝沙坦氢氯噻嗪治疗轻中度原发性高血压的疗效及安全性。方法选取轻中度原发性高血压患者80例,随机分为两组,观察组(40例)服用厄贝沙坦氢氯噻嗪治疗,对照组(40例)服用厄贝沙坦治疗,4周后根据血压决定维持原剂量或原有剂量加倍;总疗程8周。结果观察组总有效率为97.5%,对照组总有效率为82.5%,两组比较差异有统计学意义(P<0.01),两组不良反应发生率均为5%。结论厄贝沙坦氢氯噻嗪治疗轻中度高血压疗效明显,不良反应发生率低。     

厄贝沙坦氢氯噻嗪片降压疗效临床观察

目的探讨厄贝沙坦氢氯噻嗪片治疗原发性高血压的临床疗效。方法将郑州市第三人民医院2011年5月至2012年5月116例原发性高血压患者随机分为观察组和对照组各58例。观察组用厄贝沙坦氢氯噻嗪片（安博诺）治疗,对照组用厄贝沙坦片（科苏）治疗,疗程均为8周。结果观察组总有效率为93．1％,对照组总有效率为79．3％,两组比较差异有统计学意义（P〈0．05）。结论厄贝沙坦氢氯噻嗪片治疗原发性高血压效果显著,优于厄贝沙坦片治疗,值得临床借鉴。     

厄贝沙坦氢氯噻嗪片治疗原发性高血压临床观察

目的探讨厄贝沙坦氢氯噻嗪片治疗原发性高血压的临床疗效。方法将本院2009年1月至2010年7月96例高血压病患者随机分为观察组和对照组各48例。观察组用厄贝沙坦氢氯噻嗪片治疗,对照组应用厄贝沙坦治疗。疗程均为4周,疗程结束后,观察两组的治疗效果。结果观察组的总有效率为93.75%,对照组的总有效率为72.92%,两组总有效率比较差异有统计学意义(P<0.05)。结论厄贝沙坦氢氯噻嗪片治疗原发性高血压效果显著,优于厄贝沙坦治疗,值得临床借鉴。     

厄贝沙坦与厄贝沙坦氢氯噻嗪治疗糖尿病合并高血压的疗效比较

目的：评价厄贝沙坦与厄贝沙坦氢氯噻嗪对糖尿病合并高血压患者的疗效。方法选取2010年1月-2011年11月于我院门诊及住院治疗的糖尿病合并高血压患者70例,随机分为两组：A组（厄贝沙坦组,36例）口服厄贝沙坦片,1片/d;B组（厄贝沙坦氢氯噻嗪组,32例）口服厄贝沙坦氢氯噻嗪胶囊,1粒/d。4周后未达标者增加剂量1片（粒）/次,2次/d,6个月结束。结果降压效果B组优于A组（P〈0.05）。两组治疗前后的血糖、血脂及血钾浓度均差异无统计学意义。结论厄贝沙坦氢氯噻嗪比厄贝沙坦能更好地控制患者的血压,对血糖、血脂及血钾均无影响。     

厄贝沙坦氢氯噻嗪片治疗原发性高血压患者47例疗效观察

目的观察厄贝沙坦氢氯噻嗪片(安博诺)治疗原发性高血压临床疗效。方法选择北票市第一人民医院2008年5月至2009年5月原发性高血压患者90例,随机将上述患者分为观察组和对照组。其中观察组47例,对照组43例。对照组口服厄贝沙坦150mg,1次/d;观察组口服厄贝沙坦氢氯噻嗪片,每天口服1片,对血压控制不佳患者,可增加剂量,1次/d,每次2片。两组患者均用药治疗4周。结果观察组的总有效率为93.6%,对照组的总有效率为74.4%,两组总有效率比较,差异有统计学意义(P<0.05)。结论厄贝沙坦氢氯噻嗪片能够良好的控制原发性高血压患者的血压,临床治疗效果显著,值得临床推广应用。     

厄贝沙坦氢氯噻嗪片工艺验证

目的:验证厄贝沙坦氢氯噻嗪片中试工艺的可行性、可靠性。方法:按照确定的处方工艺中试生产3批样品,对工艺中的关键工艺参数进行验证。结果:验证批次的厄贝沙坦氢氯噻嗪片各项指标符合质量标准要求。结论:厄贝沙坦氢氯噻嗪片中试工艺生产可行,工艺流程及工艺参数能够保证产品质量;工艺可靠、稳定。     

厄贝沙坦氢氯噻嗪片治疗原发性高血压的疗效观察

目的比较厄贝沙坦氢氯噻嗪片与厄贝沙坦治疗轻、中度原发性高血压的临床疗效。方法将lOO傩者随机分为2组：观察组50例,厄贝沙坦氢氯噻嗪片（含厄贝沙坦150mg,氢氯噻嗪12．5mg）,1片／d;对照组50例,厄贝沙坦150mg／d。用药4周后进行疗效分析。结果观察组总有效率为98％,对照组总有效率为80％,2组比较差异有统计学意义（P〈0．05）。结论厄贝沙坦氢氯噻嗪片治疗轻、中度原发性高血压疗效优于单独使用厄贝沙坦。     

厄贝沙坦与厄贝沙坦／氢氯噻嗪复方制齐佾疗轻中度原发性高血压的疗效对比观察

目的评价厄贝沙坦与厄贝沙坦／氢氯噻嗪复方制剂治疗高血压病的疗效。方法轻中度原发性高血压患者共106例,随机分为两组,一组为厄贝沙坦治疗组（n=52）,服用厄贝沙坦150mg,1次／日;另一组为厄贝沙坦／氢氯噻嗪复方制剂组（n=54）,服用厄贝沙坦150rng和氢氯噻嗪12．5mg的复方制剂,1次／日。结果治疗12周后．厄贝沙坦／氢氯噻嗪复方制剂降压的总有效率为83．3％（45／54）,厄贝沙坦降压的总有效率为78．8％（41／52）,两组血钾、LDL-C、血糖较入组时无明显变化,组间差异无统计学意义,未观察到严重不良反应。结论厄贝沙坦／氢氯噻嗪复方制剂治疗轻中度原发性高血压患者的控制率和达标率较高．较单用厄贝沙坦未增加不良反府．     

厄贝沙坦氢氯噻嗪片治疗原发性高血压的临床评价

目的探讨厄贝沙坦氢氯噻嗪片治疗原发性高血压的临床疗效。方法收集我院已治疗原发性高血压患者108例,随机分为:观察组54例和对照组54例。观察组采用药物为厄贝沙坦氢氯噻嗪片,对照组所采用药物为厄贝沙坦。治疗完成后,观察、分析两组临床疗效。结果观察组的总有效率为94.44%,对照组的总有效率为75.93%,两组临床疗效差异有统计学意义(P<0.05)。结论在原发性高血压的治疗方面,厄贝沙坦氢氯噻嗪片的临床疗效显著优于厄贝沙坦,具有良好的临床疗效,值得推广。     

Liquid chromatographic-tandem mass spectrometric method for the simultaneous quantitation of telmisartan and hydrochlorothiazide in human plasma

A rapid and sensitive method using liquid chromatography-tandem mass spectrometry (LC-MS/MS) has been developed for the simultaneous determination of telmisartan and hydrochlorothiazide in human plasma. Sample preparation involved liquid-liquid extraction with diethyl ether-dichloromethane (60:40, v/v). The analytes and internal standard, probenecid, were separated on a Venusil XBP-C(8) column using gradient elution with acetonitrile-10 mM ammonium acetate-formic acid at a flow rate of 1.2 mL/min. Detection was by electrospray negative ionization mass spectrometry using multiple reaction monitoring of the transitions at m/z 513.0-->469.4 for telmisartan, m/z 295.9-->268.9 for hydrochlorothiazide and m/z 283.9-->239.9 for probenecid. For both analytes, the method was linear in the range 1.00-600 ng/mL with intra- and inter-day precision (as relative standard deviation) 相似文献   

Simultaneous determination of irbesartan and hydrochlorothiazide in human plasma using HPLC coupled with tandem mass spectrometry: Application to bioequivalence studies

A sensitive, specific and selective liquid chromatography/tandem mass spectrometric method has been developed and validated for the simultaneous determination of irbesartan and hydrochlorothiazide in human plasma. Plasma samples were prepared using protein precipitation with acetonitrile, the two analytes and the internal standard losartan were separated on a reverse phase C₁₈ column (50 mm × 4 mm, 3 μm) using water with 2.5% formic acid, methanol and acetonitrile (40:45:15, v/v/v (%)) as a mobile phase (flow rate of 0.70 mL/min). Irbesartan and hydrochlorothiazide were ionized using ESI source in negative ion mode, prior to detection by multiple reaction monitoring (MRM) mode while monitoring at the following transitions: m/z 296 → 269 and m/z 296 → 205 for hydrochlorothiazide, 427 → 175 for irbesartan. Linearity was demonstrated over the concentration range 0.06–6.00 μg/mL for irbesartan and 1.00–112.00 ng/mL for hydrochlorothiazide. The developed and validated method was successfully applied to a bioequivalence study of irbesartan (300 mg) with hydrochlorothiazide (12.5 mg) tablet in healthy volunteers (N = 36).     

Determination of dexmedetomidine in human plasma using high performance liquid chromatography coupled with tandem mass spectrometric detection: Application to a pharmacokinetic study

A rapid, sensitive and selective high performance liquid chromatography-electrospray ionization-tandem mass spectrometry method (HPLC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of dexmedetomidine (DMED) in human plasma. Dexmedetomidine and the internal standard (ondansetron) were extracted in a single step with diethyl-ether from 1.0 mL of alkalinized plasma. The mobile phase was a mixture of acetonitrile and 0.5% formic acid solution (30:70, v/v) at a flow rate of 0.2 mL min⁻¹. The detection was performed on a triple quadrupole tandem mass spectrometer in the selected reaction monitoring (SRM) mode using the respective [M+H]⁺ ions m/z 201.0 → 95.1 for DMED and m/z 294.1 → 170.1 for the IS. The assay exhibited a linear dynamic range of 5–5000 pg mL⁻¹ with the correlation coefficient above 0.9995. The lower limit of quantification (LLOQ) was 5 pg mL⁻¹ with a relative standard deviation of less than 15%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. The validated HPLC-MS/MS method has been successfully applied to study the pharmacokinetics of three level doses of DMED in Chinese healthy volunteers.     

厄贝沙坦与氢氯噻嗪联用在肾性高血压大鼠体内药动学-药效学关系研究

目的:应用药动学-药效学结合模型研究厄贝沙坦与氢氯噻嗪联用在肾性高血压大鼠体内单剂量及多剂量用药时的药动学-药效学关系。方法:将SD大鼠制备成2肾1夹型肾性高血压模型,给大鼠单剂量或多剂量灌胃给药,分别于第1天和第8天连续的预定时间点测定血药浓度,同时测定动脉收缩压(SBP)和动脉舒张压(DBP)等药物效应,建立效应室药动学-药效学结合模型并计算相关的药动学和药效学参数。对单用、联用及单剂量、多剂量的药动学-药效学规律进行定量研究。结果:厄贝沙坦的药动学特征呈二室模型,氢氯噻嗪在非稳态和稳态条件下均未改变厄贝沙坦的药动学参数,而在稳态条件下,厄贝沙坦可增高氢氯噻嗪的血药浓度及曲线下面积。厄贝沙坦和氢氯噻嗪联用降压效应优于单用的效应。药物效应和效应室浓度之间符合Sigmoid-Emax药效学模型。单剂量下药物效应与血药浓度间存在滞后现象,多剂量下滞后现象消失。Emax、EC50、Keo等药效学参数在厄贝沙坦组和两药联用组之间的差异有统计学意义。结论:建立了PK-PD定量数学模型研究厄贝沙坦和氢氯噻嗪联用在大鼠体内单剂量和多剂量用药后药动学-药效学(暴露-反应)关系的规律,并提供了相关的药动学和药效学参数,可为临床合理用药提供参考依据。     

Liquid chromatography tandem mass spectrometry method for simultaneous determination of antidiabetic drugs metformin and glyburide in human plasma

A simple and rapid liquid chromatography/tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the simultaneous quantitation of antidiabetic drugs metformin and glyburide in human plasma using glimepiride as internal standard (IS). After acidic acetonitrile-induced protein precipitation of the plasma samples, metformin, glyburide and IS were chromatographed on reverse phase C18 (50 mm x 4.6 mm i.d., 5 microm) analytical column. Quantitation was performed on a triple quadrupole mass spectrometer employing electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode. The total chromatographic run time was 3.5 min and calibration curves were linear over the concentration range of 20-2500 ng/ml for metformin and 5-500 ng/ml for glyburide. The method was validated for selectivity, sensitivity, recovery, linearity, accuracy and precision, dilution integrity and stability studies. The recoveries obtained for the analytes and IS (>or=69%) were consistent and reproducible. Inter-batch and intra-batch coefficient of variation across four validation runs (LLOQ, LQC, MQC and HQC) was less than 8%. The accuracy determined at these levels was within +/-8% in terms of relative error (RE). The method was applied to a bioequivalence study of 500 mg metformin and 5mg of glyburide tablet after oral administration to 28 healthy human subjects under condition of fasting.     

Determination of hydrochlorothiazide in human plasma by liquid chromatography/tandem mass spectrometry

In this study, a fast and sensitive liquid chromatography/tandem mass spectrometry method for determination of hydrochlorothiazide in human plasma was developed and validated. The analyte and irbesartan, used as the internal standard, were precipitated and extracted from plasma using methanol. Analysis was performed on a Phenomenex Kromasil C₈ column with water and methanol (27:73, v/v) as the mobile phase. Linearity was assessed from 0.78 to 200 ng/mL in plasma. The analytical method proved to be applicable in a pharmacokinetic study after oral administration of 12 mg hydrochlorothiazide tablets to 20 healthy volunteers.     

LC-ESI-MS/MS法测定人血浆中卢帕他定的浓度（英文）

目的建立测定人血浆中卢帕他定浓度的LC-ESI-MS/MS方法。方法血浆样品加入内标,碱化后用二氯甲烷：乙酸乙酯（20：80）提取,在37℃真空干燥箱中干燥至干,残渣用200μL流动相溶解后进样。色谱条件为：色谱柱为Agilent Eclipse XDB-C18（4.6mm×150mm,5μL）;流动相为乙腈（含1%甲酸）：20mmol·L^-1醋酸铵（76：24,V/V）,流速为0.6mL·min^-1。质谱条件：采用美国安捷仑1100高效液相色谱系统和离子阱（Agilent MSD Trap XCT）检测仪,质谱条件为电喷雾离子源,检测方式为正离子电离、多离子反应监测（MRM）,用于定量分析的离子为卢帕他定m/z416→309,内标氯雷他定m/z383→337。结果该方法应用于检测20名健康志愿者服药后的血浆样品。线性范围为0.05～14ng·mL^-1（r=0.998）,日内和日间精密度均低于15%,方法回收率为85.1%～114.0%。最低检测限为0.05ng·mL^-1（当n=5时,RSD=9.22%）。结论该方法灵敏、准确、快速,可用于该药药代动力学和生物等效性研究。     

Rapid quantification of nebivolol in human plasma by liquid chromatography coupled with electrospray ionization tandem mass spectrometry

A simple, sensitive and rapid liquid chromatographic/electrospray ionization tandem mass spectrometric method was developed and validated for the quantitation of nebivolol in human plasma. The method involved a simple single-step liquid–liquid extraction with diethyl ether/dichloromethane (70/30). The analyte was chromatographed on Waters symmetry^® C₁₈ reversed-phase chromatographic column by isocratic elution with water:acetonitrile:formic acid (30:70:0.03, v/v) and analyzed by mass spectrometry in the multiple reaction monitoring mode. The precursor to product ion transitions of m/z 406.4–151.5 and m/z 409.1–228.1 were used to measure the analyte and the internal standard (I.S.), respectively. The chromatographic runtime was 2 min and the weighted (1/x²) calibration curves were linear over the range 50–10,000 pg/mL. The method was validated in terms of accuracy, precision, absolute recovery, freeze-thaw stability, bench-top stability and re-injection reproducibility. The limit of detection and lower limit of quantification in human plasma were 10 and 50 pg/mL, respectively. The within- and between-batch accuracy and precision were found to be well within acceptable limits (<10%). The analyte was stable after three freeze-thaw cycles (deviation <10%). The average absolute recoveries of nebivolol and tamsulosin, used as an internal standard, from spiked plasma samples were 73.4 ± 3.7 and 72.1 ± 2.0%, respectively. The assay method described here was applied to study the pharmacokinetics of nebivolol.     

厄贝沙坦与氢氯噻嗪联合治疗原发性高血压的疗效和安全性评价

目的 :观察厄贝沙坦(国产)与氢氯噻嗪治疗1、2级原发性高血压的疗效和安全性。方法 :73例1、2级原发性高血压患者随机分成两组 ,分别服用厄贝沙坦150mg日1次与氢氯噻嗪12 5mg日1次和卡托普利25mg日3次与氢氯噻嗪12 5mg日1次 ,治疗4周。观察用药前后血压、心率变化 ,记录患者用药的不良反应 ,结合实验室检查作安全性评价。结果 :两组治疗前后相比 ,血压下降差异有非常显著性(P<0 01)。厄贝沙坦组总有效率为80 6% ,卡托普利组为77 1% ,两组间比较差异无显著性(P>0 05) ,但药物相关不良反应前者显著低于后者(P<0 05)。结论 :厄贝沙坦与氢氯噻嗪联合应用治疗1、2级原发性高血压疗效确切 ,患者耐受性和安全性较好