How to Set Your Target Limit of Quantification

One of the key things to do during the transition from preclinical development studies to clinical development studies is to set the target for your drug assay limit of quantification (LOQ). I will outline a few considerations on that topic. Here are my main assumptions:

1. You are working with a drug that is intended for systemic delivery (not a local drug like topical dermatological or ophthalmic)
2. You have some exposure data from preclinical species
3. You have estimated a peak human exposure using some method (eg, allometry)

To set your target LOQ, you use the expected peak human exposure. Let’s assume the following for our example:

Predicted C_max = 250 ng/mL

You will need at least 5 half-lives after the peak occurs to accurately calculate the terminal elimination rate constant. You can calculate how much drug remains after 5 half-lives using the following equation:

This gives a reasonable estimate for the LOQ. In this case, I would round down to 1 ng/mL as my initial target LOQ with a stretch goal of trying to achieve 0.1 ng/mL in case my human prediction was high.

That’s all there is to it!

表征化合物药代动力学（PK）和药效学（PD）的方法可能本身就很复杂和精密。PK/PD 分析是一门科学，需要数学和统计学背景以及对生物学、药理学和生理学的了解。PK/PD 分析为药物开发中的关键决策提供指导，如优化剂量、频率和暴露持续时间，因此正确做出这些决策至关重要。选择决策工具同样重要。幸运的是，PK/PD 分析软件近年来有了很大的发展，使用户可以专注于分析，而不是算法和编程语言。阅读我们的白皮书，了解选择 PK/PD 分析软件时的主要考虑因素。