Albany College of Pharmacy and Health Sciences, Department of Pharmaceutical Sciences, 106 New Scotland Avenue, Albany, NY 12208, USA.
Albany College of Pharmacy and Health Sciences, Department of Pharmacy Practice, 106 New Scotland Avenue, Albany, NY 12208, USA.
J Pharm Sci. 2021 Mar;110(3):1401-1411. doi: 10.1016/j.xphs.2020.12.001. Epub 2020 Dec 8.
Most quantitative research methods are based on measuring either the total or the free concentration of an analyte in a sample. However, this is often insufficient for the study of complex biological systems. The main objective of this research was to develop new methods for providing more information from samples: the free concentration (C), the total concentration (C), and the plasma binding capacity (PBC). Samples were processed using microextraction and ultrafiltration. For each of these techniques, two quantification procedures were used: addition of isotopically labeled standard and repeated analysis of the same sample. The new methods were validated by analyzing clinical samples and samples with known concentrations. Methods based on addition of labeled compound were found to be the fastest, and most reproducible. For analysis of clinical samples, methods based on microextraction were more sensitive and more accurate than those based on ultrafiltration. For analysis of pooled plasma samples, the overall accuracy of all approaches to determine PBC, testosterone C, and testosterone C was between 94 and 109%, 87-113%, and 94-122% respectively. The new approach goes beyond a simple concentration measurement, giving more information from clinical samples, with great potential for personalizing drug dosage and therapy to the needs of individual patients.
大多数定量研究方法都基于测量样品中分析物的总浓度或游离浓度。然而，这对于研究复杂的生物系统往往是不够的。本研究的主要目的是开发新的方法，从样品中提供更多信息：游离浓度（C）、总浓度（C）和血浆结合能力（PBC）。使用微萃取和超滤法对样品进行处理。对于每种技术，使用两种定量程序：添加同位素标记的标准品和重复分析同一样品。通过分析临床样品和已知浓度的样品对新方法进行了验证。添加标记化合物的方法被发现最快且最可重现。对于临床样品的分析，基于微萃取的方法比基于超滤的方法更灵敏、更准确。对于混合血浆样品的分析，确定 PBC、睾酮 C 和睾酮 C 的所有方法的总准确度分别在 94%至 109%、87%至 113%和 94%至 122%之间。新方法超越了简单的浓度测量，从临床样品中提供了更多信息，具有根据个体患者的需求为药物剂量和治疗方案实现个体化的巨大潜力。
