The use of human plasma as matrix for calibration standards in pre-clinical LC-MS/MS methods--a way to reduce animal use.
The option, for practical and ethical reasons, to replace animal plasma with human plasma for calibration standards was successfully applied to 73 analytical methods developed in our laboratory during the last years. The animals used for obtaining blank plasma could then be reduced with a number corresponding to about 25% of mice or 5% of rats in ordinary one-month toxicology studies. This is of important public concern and also in accordance with the 3R-strategy. The methods were successfully validated for determination of drug concentrations in plasma from rat, dog, mouse, rabbit and cynomolgus monkey. Reproducibility of study samples from dosed animals was established, showing a mean accuracy of 100.8% with a CV of 7.2% (n=1339). The purpose of this paper is to present a scientific basis for the alternative approach to adopt human plasma matrix for calibration standards, which will reduce animal use, without compromising the quality of appropriately validated assays. Additional advantages are cheaper and simplified plasma maintenance and the possibility to validate methods for several species in the same analytical batch.
Clinical Pharmacology & DMPK, AstraZeneca R&D Mölndal, SE-431 83 Mölndal, Sweden. britt-marie.jacobson@astrazeneca.com
Britt-Marie
BM
Jacobson
Anders
A
Olsson
Christina
C
Fakt
Daniel
D
Öhman
D000826:Animal Testing Alternatives; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D004353:Drug Evaluation, Preclinical / Q000191:economics / Q000379:methods*; D004355:Drug Stability; D015507:Drugs, Investigational / Q000032:analysis*; D006801:Humans; D004364:Pharmaceutical Preparations / Q000097:blood*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D018675:Toxicity Tests / Q000191:economics / Q000379:methods
D015507:Drugs, Investigational; D004364:Pharmaceutical Preparations