Toward Analytical Performance Specifications for Immunosuppressive Drug Quantification in Transplantation: An Opinion...

Area of Science:

• Clinical Chemistry
• Pharmacology
• Analytical Science

Background:

• Analytical method performance is critical for clinical needs in drug monitoring.
• Establishing permissible analytical imprecision goals (pCVA%) is essential for reliable drug analysis.
• Various approaches exist for setting pCVA%, necessitating a comparative evaluation.

Purpose of the Study:

• To calculate pCVA% for key immunosuppressant drugs using four distinct methodologies.
• To compare the outcomes of these different approaches for setting analytical goals.
• To critically discuss the advantages and disadvantages of each evaluated model.

Main Methods:

• Four approaches were used: biological variation, drug elimination half-life/dosing interval, and two therapeutic range (TR)-based methods.
• Routine measurement data from 2022-2023 were analyzed for biological variation.
• Liquid chromatography-tandem mass spectrometry and electrochemiluminescence immunoassays were employed for specific drug analyses.

Main Results:

• All four approaches produced comparable pCVA% values for the studied drugs.
• Average pCVA% ranged from 4.8% (sirolimus) to 7.7% (mycophenolic acid).
• TR-based approaches presented the most challenging goals, while biological variation was most achievable; longer half-life drugs required more stringent goals.

Conclusions:

• No single ideal method exists for setting drug analysis goals.
• The calculated pCVA% values support a <6% target as adequate and realistic for modern drug monitoring.
• TR-based approaches are preferred for their clinical relevance and integration of biological and analytical factors.