Ahmed Sameh, Atia Noha N, Bakr Ali Marwa Fathy
Pharmacognosy and Pharmaceutical Chemistry Department, College of Pharmacy Taibah University, Al Madinah AlMunawarah 30001, Saudi Arabia; Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Assiut University, Assiut 71526, Egypt.
J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Mar 1;1046:200-210. doi: 10.1016/j.jchromb.2017.01.034. Epub 2017 Jan 27.
Felodipine (FLD), a calcium channel antagonist, is commonly prescribed for the treatment of hypertension either with Metoprolol (MET) or Ramipril (RAM) in two different drug combinations. FLD has high plasma protein binding ability affecting its extraction recoveries from plasma samples. Hence, a specific ultrasound assisted dispersive liquid-liquid microextraction (UA-DLLME) method coupled with HPLC using photodiode array detector was developed and validated for the simultaneous determination of FLD, MET and RAM in rat plasma after oral administration of these combinations. The factors affecting UA-DLLME were carefully optimized. In this study, UA-DLLME method could provide simple and efficient plasma extraction procedures with superior recovery results. Under optimum condition, all target drugs were separated within 13min. The validation procedures was carried out in agreement with US-FDA guidelines and shown to be suitable for anticipated purposes. Linear calibration ranges were obtained in the range 0.05-2.0μgmL for FLD and MET and 0.1-2.0μgmL for RAM with detection limits of 0.013-0.031μgmL for all the studied drug combinations. The%RSD for inter-day and intra-day precisions was in range of 0.63-3.85% and the accuracy results were in the range of 92.13-100.5%. The validated UA-DLLME-HPLC method was successfully applied for the bioavailability studies of FLD, MET and RAM. The pharmacokinetic parameters were calculated for all the investigated drugs in rats after single-dose administrations of two different drug combinations. Although FLD was bioequivalent in the two formulations, a small increase in plasma levels of MET and RAM was found in the presence of FLD.
非洛地平（FLD）是一种钙通道拮抗剂，常用于与美托洛尔（MET）或雷米普利（RAM）以两种不同的药物组合治疗高血压。非洛地平具有较高的血浆蛋白结合能力，这会影响其从血浆样品中的提取回收率。因此，开发并验证了一种特定的超声辅助分散液液微萃取（UA-DLLME）方法，该方法与使用光电二极管阵列检测器的高效液相色谱法联用，用于同时测定大鼠口服这些组合药物后血浆中的非洛地平、美托洛尔和雷米普利。仔细优化了影响UA-DLLME的因素。在本研究中，UA-DLLME方法可以提供简单有效的血浆提取程序，并具有优异的回收率结果。在最佳条件下，所有目标药物在13分钟内分离。验证程序按照美国食品药品监督管理局（US-FDA）的指南进行，结果表明适用于预期目的。非洛地平和美托洛尔的线性校准范围为0.05 - 2.0μg/mL，雷米普利的线性校准范围为0.1 - 2.0μg/mL，所有研究药物组合的检测限为0.013 - 0.031μg/mL。日间和日内精密度的相对标准偏差（%RSD）在0.63 - 3.85%范围内，准确度结果在92.13 - 100.5%范围内。经过验证的UA-DLLME-HPLC方法成功应用于非洛地平、美托洛尔和雷米普利的生物利用度研究。计算了大鼠单次给药两种不同药物组合后所有研究药物的药代动力学参数。尽管非洛地平在两种制剂中生物等效，但在非洛地平存在的情况下，发现美托洛尔和雷米普利的血浆水平略有升高。
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