How to Set Your Target Limit of Quantification

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 Cmax = 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:

 C_{remaining}=C_{max}*\frac{1}{2}^5

 C_{remaining}=7.8125 ng/mL

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!

The methods used to characterize the pharmacokinetics (PK) and pharmacodynamics (PD) of a compound can be inherently complex and sophisticated. PK/PD analysis is a science that requires a mathematical and statistical background, combined with an understanding of biology, pharmacology, and physiology. PK/PD analysis guides critical decisions in drug development, such as optimizing the dose, frequency and duration of exposure, so getting these decisions right is paramount. Selecting the tools for making such decisions is equally important. Fortunately, PK/PD analysis software has evolved greatly in recent years, allowing users to focus on analysis, as opposed to algorithms and programming languages. Read our white paper to learn about the key considerations when selecting software for PK/PD analysis.

Nathan Teuscher

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Nathan Teuscher

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Dr. Nathan Teuscher is the Vice President of Pharmacometric Solutions at Certara. He is an expert in clinical pharmacology, pharmacometrics, pharmacokinetics and pharmacodynamics and was trained by David Smith at the University of Michigan. Dr. Teuscher has held leadership positions in biotechnology, pharmaceutical and contract research companies. In 2008 he established the Learn PKPD.com website to share his knowledge with the community. Prior to coming to Certara, he was the Founder and President of PK/PD Associates.