Endocrine Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Department of Internal Medicine, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran.
BMC Pharmacol Toxicol. 2024 Aug 8;25(1):45. doi: 10.1186/s40360-024-00773-3.
Concentrations of metoprolol in exhaled breath condensate (EBC) have not been investigated. Herein, we aim to determine the metoprolol levels in EBC, plasma, and urine samples.
Biological samples were collected from 39 patients receiving metoprolol. Metoprolol was determined using liquid chromatography mass spectrometery. The obtained metoprolol levels in biological fluids were investigated for possible inter-correlations.
Acceptable linearity was obtained with coefficient of determinations equal to 0.9998, 0.9941, and 0.9963 for EBC, plasma, and urine samples, respectively. The calibration curves were linear in the ranges of 0.6-500, 0.4-500, and 0.7-10,000 µg·L regarding EBC, plasma, and urine samples, respectively. The detection and quantification limits were (0.18, 0.12, and 0.21 µg·L) and (0.60, 0.40, and 0.70 µg·L) for EBC, plasma, and urine samples, respectively. The relative standard deviations for the intra- and inter-day replications were obtained between 5.2 and 6.1 and 3.3-4.6%, respectively. The obtained mean metoprolol levels in EBC, plasma, and urine samples of 39 patients were 5.35, 70.76, and 1943.1 µg·L. There were correlations between daily dose and plasma and urinary concentrations of metoprolol in the investigated samples, whereas no significant correlation was observed for daily dose and EBC levels. The correlation among plasma-urine levels was significant, however, the non-significant correlation was obtained between plasma and EBC concentrations.
Metoprolol levels varied widely due to the metabolic pattern of the Azeri population, different dosages received by the patients, formulation effects, age, sex, and interactions with the co-administered drugs. A poor correlation of EBC-plasma concentrations and a significant correlation of plasma-urine concentrations were observed. Further investigations are required to provide the updated services to personalized medicine departments.
尚未研究过呼气冷凝物(EBC)中美托洛尔的浓度。在此,我们旨在确定 EBC、血浆和尿液样本中的美托洛尔水平。
从接受美托洛尔治疗的 39 名患者中采集生物样本。使用液质联用仪测定美托洛尔。对生物体液中获得的美托洛尔水平进行了可能的相互关联研究。
EBC、血浆和尿液样本的测定系数分别为 0.9998、0.9941 和 0.9963,均具有可接受的线性。EBC、血浆和尿液样本的校准曲线分别在 0.6-500、0.4-500 和 0.7-10000μg·L 的范围内呈线性。EBC、血浆和尿液样本的检测限和定量限分别为(0.18、0.12 和 0.21μg·L)和(0.60、0.40 和 0.70μg·L)。日内和日间重复的相对标准偏差分别为 5.2-6.1%和 3.3-4.6%。从 39 名患者的 EBC、血浆和尿液样本中获得的平均美托洛尔水平分别为 5.35、70.76 和 1943.1μg·L。在所研究的样本中,美托洛尔的日剂量与血浆和尿液浓度之间存在相关性,而 EBC 水平与日剂量之间无显著相关性。血浆-尿液水平之间存在相关性,但是血浆和 EBC 浓度之间相关性不显著。
由于阿塞拜疆人群的代谢模式、患者接受的不同剂量、制剂效应、年龄、性别以及与合并用药的相互作用,美托洛尔水平差异很大。EBC-血浆浓度相关性差,而血浆-尿液浓度相关性显著。需要进一步的研究为个体化医学部门提供最新的服务。