Duggan Jeffrey X
JXD Bioanalytics, 159 Lakemere Drive, Southbury, CT 06488, USA.
Bioanalysis. 2019 Apr;11(8):797-814. doi: 10.4155/bio-2018-0261. Epub 2019 Apr 17.
In response to an earlier workshop covering the pros and cons of quantification below the LLOQ (BLQ) the author reviews the topics discussed from the bioanalytical standpoint. Important considerations for estimating concentrations below the LLOQ include: method signal-to-noise, baseline shape and condition, close lying interference peaks (especially for protein methods), matrix effect, adsorption and stability of the analyte at low concentrations and carryover. These methodological issues are discussed as possible contributors to inaccuracy in BLQ estimations, and appropriate cautions are provided via examples. A proposed method for the evaluation of BLQ estimations utilizes extended incurred sample reanalysis analysis where BLQ samples or spiked simulated samples are analyzed with quality controls and standards in addition to those in the original study. Generally, BLQ estimations are discouraged, with the recommendation that any extrapolations should be done in close collaboration between the pharmacokinetic (PK) and bioanalytical scientists in consultation with the regulatory agency.
针对之前一个讨论定量下限（LLOQ）以下定量（低于定量下限，BLQ）利弊的研讨会，作者从生物分析的角度回顾了所讨论的主题。估计低于LLOQ浓度时的重要考虑因素包括：方法的信噪比、基线形状和状况、紧邻的干扰峰（特别是对于蛋白质方法）、基质效应、低浓度下分析物的吸附和稳定性以及残留。这些方法学问题被讨论为可能导致BLQ估计不准确的因素，并通过实例给出了适当的注意事项。一种评估BLQ估计的建议方法利用扩展的已发生样品再分析，除了原始研究中的样品外，还使用质量控制样品和标准品对BLQ样品或加标模拟样品进行分析。一般来说，不鼓励进行BLQ估计，建议任何外推都应在药代动力学（PK）和生物分析科学家与监管机构密切协商的情况下进行。
