Flow and Sequential Injection Manifolds for the Spectrophotometric Determination of Captopril Based on its Oxidation by Fe(III)

 Two new simple and rapid methods are reported for the accurate and precise spectrophotometric determination of captopril (CPL) using flow (FI) and sequential injection (SI) analysis. The methods are based on the fast oxidation of CPL by Fe(III). The produced Fe(II) reacts with 2,2′-dipyridyl-2-pyridylhydrazone (DPPH) in acidic medium to form a colored complex which is monitored spectrophotometrically at 535 nm. Both methods allow the determination of the analyte up to 1000 mg L⁻¹ at a sampling rate of 120 and 60 injections per hour for FI and SI, respectively. The methods are very precise [s _r=0.8 and 1.2% at 500 mg L⁻¹ CPL (n=12) for FI and SI, respectively] and the 3σ detection limits (c _L=4.0 and 7.0 mg L¹, respectively) are quite satisfactory. Their application to a variety of anti-hypertensive commercial pharmaceutical formulations showed excellent results (relative errors, e _r, < ± 1.6% in all cases compared to an official HPLC method), while common pharmaceutical excipients were found not to interfere. Recovery experiments further verified the accuracy of the developed methods, as the percent recoveries were in the range of 98.1–102.5%. Author for correspondence. E-mail: themelis@chem.auth.gr Received May 9, 2002; accepted January 8, 2003 Published online May 5, 2003     

Assay of free captopril in human plasma as monobromobimane derivative,using RPLC/(+)ESI/MS/MS: validation aspects and bioequivalence evaluation

A sensitive method for determination of free captopril as monobromobimane derivative in plasma samples is discussed. The internal standard (IS) was 5‐methoxy‐1H‐benzimidazole‐2‐thiol. Derivatization with monobromobimane immediately after blood collection and plasma preparation prevents oxidation of captopril to the corresponding disulfide compound and enhances the ionization yield. Consequently, derivatization enhances sample stability and detection sensitivity. Addition of the internal standard was made immediately after plasma preparation. The internal standard was also derivatized by monobromobimane, as it contains a thiol functional group. Preparation of plasma samples containing captopril and IS derivatives was based upon protein precipitation through addition of acetonitrile, in a volumetric ratio 1:2. The reversed‐phase liquid chromatographic separation was achieved on a rapid resolution cartridge Zorbax SB‐C₁₈, monitored through positive electrospray ionization and tandem MS detection using the multiple‐reaction monitoring mode. Transitions were 408–362 amu for the captopril derivative and 371–260 amu for the internal standard derivative. The kinetics of captopril oxidation to the corresponding disulfide compound in plasma matrix was also studied using the proposed method. A linear log–log calibration was obtained over the concentration interval 2.5–750 ng/mL. A low limit of quantitation in the 2.5 ng/mL range was obtained. The analytical method was fully validated and successfully applied in a three‐way, three‐period, single‐dose (50 mg), block‐randomized bioequivalence study for two pharmaceutical formulations (captopril LPH 25 and 50 mg) against the comparator Capoten 50 mg. Copyright © 2009 John Wiley & Sons, Ltd.     

基于Discovery Studio软件的本科生创新实验项目设计*——卡托普利与血管紧张素转化酶的分子对接

基于Discovery Studio软件高质量的分子三维结构可视化功能和分子对接模拟模块,设计了卡托普利与血管紧张素转化酶的分子对接实验,让学生通过分子对接模拟过程,掌握药物分子结构特征,理解构效关系特征,认识酶抑制剂和靶蛋白的作用机制,了解药物研究新手段。     

离子色谱法测定复方卡托普利片中卡托普利和氢氯噻嗪的含量

建立离子色谱法测定复方卡托普利片中卡托普利和氢氯噻嗪含量的方法。在色谱柱为IonPacSCS1(4mm×250mm),保护柱为IonPacSCG1(4mm×50mm),淋洗液为甲烷磺酸(4mmol/L)+乙腈(26%),流速1.0mL/min,柱温35℃,进样量7μL,紫外检测波长215nm的条件下,测定结果表明,卡托普利和氢氯噻嗪在0.5～25μg/mL范围内线性关系良好,相关系数r分别为0.9997、0.9999,回收率分别为98.11%、94.24%。方法操作简单,灵敏度高、准确、重现性好,可用于复方卡托普利片的质量控制。     

荧光反猝灭法测定药剂中卡托普利

建立荧光反猝灭法测定卡托普利(CAT)的体系。碘(I-3)与罗丹明B(RhB)缔合作用使罗丹明B荧光信号强度减弱直至荧光猝灭,而卡托普利可将I-3还原为I-,使体系荧光信号再现。在2~20μmol·L^-1范围内荧光强度再现值ΔF与卡托普利浓度有线性关系:ΔF=-8.438+10.774 c(r=0.9986),检出限为3.34×10^-9 mol·L^-1。方法用于药剂卡托普利含量测定,测定值与标示量一致,加标回收率在95.2%~102.3%之间。     

流动注射在线过滤稀释原子吸收法测定药物制剂中卡托普利

提出了卡托普利的FI-AAS分析新方法。它是基于在适当酸度条件下卡托普利将Cu^2 还原为Cu^ ，新生的Cu^ 与SCN^-生成白色沉淀，经流动注射在线过滤稀释，以AAS法测定反应剩余Cu^2 的量来间接测定卡托普利的量。在2～100mg/L范围内呈良好的线性关系，回收率为97.1%～99.5%，采样频率为100h^-1。方法简单、快速、选择性好，节省试剂，用于卡托普利的测定，获得满意结果。     

卡托普利缓释片释放过程的灰色数学模型

目的:用灰色理论研究卡托普利缓释片的体外释放过程.方法:采用羧甲基纤维素钠为骨架材料制备缓释片,通过体外释放试验,根据灰色数学模型,预测卡托普利缓释片的体外释放过程.结果:预测值与实测值的平均绝对误差E为0.532,平均相对误差为1.059%.结论:为卡托普利缓释片的临床合理化用药提供了理论依据.     

灰色GM[1,1,t~(1/2)]模型及在药动学中的应用

将灰色理论用于人体药物代谢动力学的研究 ,建立了一种新的灰色模型 GM 1 ,1 ,t ,适合于那些单峰形态的原始数据列 .并根据抗高血压药复方卡托普利片的血药浓度给出了灰色药物动力模型 .结果表明 ,精度优于传统的一室模型 ,而且所用参数少 ,便于计算 .灰色理论可用于药物动力学中单峰序列的研究 .     

Magnetic molecularly imprinted polymer based on dynamically established metal-mediated binding sites for the determination of trace captopril in rat plasma

Therapeutic drug monitoring of captopril, which is a commonly used antihypertensive agent in clinical practice, is necessary. However, matrix effect-induced pretreatment is the bottleneck for determination. Metal-mediated molecularly imprinted polymers, an essential branch of molecularly imprinted polymers with better specificity and selectivity, have been used to separate/enrich analytes from complex matrices. In this work, Cu²⁺ was introduced to dynamically establish the binding sites of metal-mediated molecularly imprinted polymer towards captopril. All evidence demonstrated that the metal-mediated molecularly imprinted polymer based on Cu²⁺ coordination obtained a higher adsorption capacity (81.23 mg/g), faster adsorption rate (adsorption equilibrium within 50 min), and better selectivity (with the unrecognized analog). Subsequently, the Cu²⁺-mediated molecularly imprinted polymer was used as dispersive molecularly imprinted solid-phase extraction to successfully establish an analytical platform for the determination of trace captopril in rat plasma. The enrichment factor was up to 20, the detection limit was as low as 0.16 μg/ml, and the average recovery was in the range of 87.51%–98.28% with a relative standard deviation of less than 3.29%. This study provides a promising reference for the preparation of selective adsorbents to improve pretreatment.