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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!

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About the author

Nathan Teuscher
By: Nathan Teuscher
Dr. Teuscher has been involved in clinical pharmacology and pharmacometrics work since 2002. He holds a PhD in Pharmaceutical Sciences from the University of Michigan and has held leadership roles at biotechnology companies, contract research organizations, and mid-sized pharmaceutical companies. Prior to joining Certara, Dr. Teuscher was an active consultant for companies and authored the Learn PKPD blog for many years. At Certara, Dr. Teuscher developed the software training department, led the software development of Phoenix, and now works as a pharmacometrics consultant. He specializes in developing fit-for-purpose models to support drug development efforts at all stages of clinical development. He has worked in multiple therapeutic areas including immunology, oncology, metabolic disorders, neurology, pulmonary, and more. Dr. Teuscher is passionate about helping scientists leverage data to aid in establishing the safety and efficacy of therapeutics.

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