Salting‐out‐assisted liquid–liquid extraction with acetonitrile for the determination of trimetazidine in rat plasma using liquid chromatography–mass spectrometry

A high‐throughout bioanalytical method based on salting‐out‐assisted liquid/liquid extraction (SALLE) method with acetonitrile and mass spectrometry‐compatible salts followed by LC‐MS/MS analysis of trimetazidine in rat plasma is presented. It required only 50 μL of plasma and allows the use of minimal volumes of organic solvents. The seamless interface of SALLE and LC‐MS eliminated the drying‐down step and the extract was diluted and injected into an LC‐MS/MS system with a cycle time of 2.5 min/sample. The retention times of trimetazidine and IS were approximately 1.1 and 1.7 min, respectively. Calibration curves were linear over the concentration range of 0.1–100 ng/mL, which can be extended to 500 ng/mL by dilution. The intra‐ and inter‐batch precision, accuracy and the relative standard deviation were all <15%. This method was successfully applied to determine trimetazidine concentrations in rat plasma. Copyright © 2014 John Wiley & Sons, Ltd.     

Overcoming interference of plasma phospholipids using HybridSPE for the determination of trimetazidine by UPLC–MS/MS

An improved, precise and reliable ultra‐performance liquid chromatography–tandem mass spectrometry (UPLC–MS/MS) method has been developed for the quantification of trimetazidine, using trimetazidine‐d8 as the internal standard (IS). Interference owing to plasma phospholipids during sample preparation was overcome using a hybrid solid‐phase extraction–phospholipid ultra cartridge. The mean extraction recovery of trimetazidine (98.66%) and trimetazidine‐d8 (97.63%) from spiked plasma was consistent and reproducible. Chromatographic analysis was performed on a UPLC Ethylene Bridged Hybrid (BEH) C18 (50 × 2.1 mm, 1.7 μm) column with isocratic elution using acetonitrile–5 mm ammonium formate, pH 3.5 (40:60, v/v) as the mobile phase. The parent → product ion transitions for trimetazidine (m/z 267.1 → 181.1) and trimetazidine‐d8 (m/z 275.2 → 181.1) were monitored on a triple quadrupole mass spectrometer with electrospray ionization functioning in the positive multiple reaction monitoring mode. The linearity of the method was established in the concentration range of 0.05–100 ng/mL for trimetazidine. The intra‐batch and inter‐batch accuracy and precision (CV) were 97.3–103.1 and 1.7–5.3%, respectively. Qualitative and quantitative assessment of matrix effect showed no interference of endogenous/exogenous components. The developed method was used to measure plasma trimetazidine concentration for a bioequivalence study with 12 healthy subjects.     

Non-extractive procedure followed by LC/APCI MS/MS analysis of trimetazidine in plasma samples for assessing bioequivalence of immediate/modified release formulations

Trimetazidine and internal standard [1-(2,4,5-trimethoxybenzyl)piperazine] were isolated from plasma by protein precipitation with trifluoroacetic acid. The neutralized supernatant was separated on a C(8) column with methanol-aqueous 0.11% triethylamine adjusted to pH 3.3 with formic acid (1:4, v/v) at a flow rate of 0.85 mL/min. The separation was achieved within 8 min and the column ef fluent was transferred into an ion trap analyzer via an atmospheric pressure chemical ionization interface. The mass analyzer was used in the selected reaction monitoring mode, to enhance detection selectivity. The method was fully validated with a quantitation limit for trimetazidine of 1.5 ng/mL. The method was successfully applied to assess bioequivalence of two immediate and two modified commercially available pharmaceutical formulations containing 20 and 35 mg of trimetazidine, respectively.     

Hollow fiber‐based liquid membrane microextraction combined with high‐performance liquid chromatography for extraction and determination of trimetazidine in human plasma

A hollow fiber‐based liquid phase microextraction strategy combined with high‐performance liquid chromatography was evaluated for the quantitative determination of trimetazidine in human plasma. Trimetazidine was extracted from a 2.1 mL basified plasma sample (donor phase) into the organic solvent (n‐octanol) impregnated in the pores of a hollow fiber and then extracted into an acidic solution (acceptor phase) inside the lumen of the hollow fiber. The result showed that transport of drugs from alkaline sample solution into 0.5 m HCl occurred efficiently when 25 μL of 250 mm sodium 1‐octanesulfonate was added into the donor phase. Several parameters influencing the efficiency of the method, such as the nature of organic solvent used to impregnate the membrane, compositions of donor phase and acceptor phase, type and concentration of carrier, extraction time, stirring rate and salt concentration, were investigated and optimized. Under the optimal conditions, the calibration curves were obtained in the range of 5–200 ng/mL with reasonable linearity (r > 0.9980). The method was successfully applied to determine the concentration of trimetazidine in human plasma. Copyright © 2012 John Wiley & Sons, Ltd.     

曲美他嗪在冠心病合并心力衰竭治疗中的应用价值探究

目的分析并研究曲美他嗪在冠心病合并心力衰竭患者治疗中的应用价值。方法选取2015年3月至2016年3月期间上饶市广丰区人民医院收治的冠心病合并心力衰竭患者86例,按照随机数字表抽取法均分成对照组和观察组,每组各43例,其中对照组患者采用常规疾病内科治疗方式,观察组在对照组治疗的基础上增加曲美他嗪治疗,观察比较两组患者的治疗效果及治疗前后左室舒张期末内径和左室收缩期末内径及左室射血分数。结果观察组患者治疗有效率为95.34%,对照组患者治疗有效率为81.40%,数据比较差异具有统计学意义(P0.05);治疗后,观察组患者左室舒张期末内径、左室收缩期末内径显著低于对照组,左室射血分数显著高于对照组,数据比较差异具有统计学意义(P0.05)。结论对冠心病合并心力衰竭患者在常规治疗的基础上增加曲美他嗪具有显著的效果,且安全性较高,具有重要的临床价值。     

美托洛尔联合曲美他嗪治疗冠心病心力衰竭患者临床疗效观察

目的探讨临床应用美托洛尔联合曲美他嗪治疗冠心病心力衰竭的治疗效果。方法将汉川市人民医院2014年1月—2015年1月收治的120例冠心病心力衰竭患者,经患者及家属同意,伦理委员会批准,按数字分组法随机分为对照组与观察组,每组60例患者,观察组单一采用美托洛尔治疗,对照组在观察组的基础上,加用联合曲美他嗪治疗。疗程为6个月,对比两组的心脏各项功能的改善情况及治疗效果。结果对照组总有效率为96.6%(58/60),明显高于观察组的66.6%(40/60)(P0.05)。对照组治疗后心率、收缩压和左心室射血等方面均优于观察组,(P0.05)。结论临床上应用美托洛尔联合盐酸曲美他嗪治疗疗冠心病并发心力衰竭,安全有效,对改善患者心功能效果显著,值得推广。