Center for Molecular Signaling (PZMS), Institute of Experimental and Clinical Pharmacology and Toxicology, Department of Experimental and Clinical Toxicology, Saarland University, 66421 Homburg, Germany.
Klinik für Innere Medizin III, Kardiologie, Angiologie und Internistische Intensivmedizin, Universitätsklinikum des Saarlandes, Saarland University, 66421 Homburg, Germany.
Molecules. 2021 Mar 9;26(5):1495. doi: 10.3390/molecules26051495.
Poor adherence to antihypertensive drug therapy is a well-recognized problem and can be assessed by mass spectrometry-based analyses of body fluids. However, contrary statements exist whether drug quantification in blood or qualitative screening in urine is more suitable. The present pilot study aimed to further elucidate the power of blood plasma drug concentrations for adherence monitoring by developing and validating a quantification procedure for nine antihypertensive drugs (amlodipine, bisoprolol, candesartan, canrenone, carvedilol, metoprolol, olmesartan, torasemide, and valsartan) in blood plasma using liquid-liquid extraction and an ultra-high-performance liquid chromatography-ion trap mass spectrometry analysis. The procedure should then be used for an adherence assessment and compared with the results of an established qualitative urine screening. Selectivity, carryover, matrix effect, accuracy, precision, dilution integrity, and stability were successfully validated, except for amlodipine. The applicability was demonstrated by analyzing 19 plasma samples containing 28 antihypertensive drugs and comparing the measured concentrations with calculated dose-dependent reference plasma concentration ranges. The interpretation of plasma concentrations was found to be more sophisticated and time-consuming than that of urine screening results, and adherence could not be assessed in two cases (10%) due to measured plasma concentrations below the lower limit of quantification. However, 14 out of 19 subjects were classified as adherent (75%) and three as nonadherent (15%), in contrast to 19 (100%) that were claimed to be adherent based on the results of the qualitative urine screening. Nevertheless, further data is needed to estimate whether plasma quantification is superior in terms of assessing adherence to antihypertensive medication.
抗高血压药物治疗的依从性差是一个众所周知的问题，可以通过基于质谱分析的体液分析来评估。然而，关于血液中的药物定量分析和尿液中的定性筛选哪种更适合的说法却存在矛盾。本研究旨在通过开发和验证一种用于检测九种抗高血压药物（氨氯地平、比索洛尔、坎地沙坦、坎地沙坦酮、卡维地洛、美托洛尔、奥美沙坦、托拉塞米和缬沙坦）在血浆中的浓度的定量程序，进一步阐明血液药物浓度在药物依从性监测中的作用，该程序使用液液萃取和超高效液相色谱-离子阱质谱分析。然后，该程序将用于进行药物依从性评估，并与已建立的定性尿液筛选结果进行比较。除了氨氯地平，该程序的选择性、交叉污染、基质效应、准确度、精密度、稀释完整性和稳定性均得到了成功验证。通过分析 19 个含有 28 种抗高血压药物的血浆样本，并将测量浓度与计算的剂量依赖性参考血浆浓度范围进行比较，证明了该方法的适用性。与尿液筛选结果相比，对血浆浓度的解释更为复杂和耗时，由于测量的血浆浓度低于定量下限，有两个案例（10%）无法进行药物依从性评估。然而，与基于定性尿液筛选结果声称的 19 名（100%）受试者均为依从者相比，19 名受试者中有 14 名（75%）被归类为依从者，3 名（15%）为不依从者。然而，需要进一步的数据来评估血浆定量在评估抗高血压药物依从性方面是否具有优势。
