Institutional members access full text with Ovid®

Share this article on:

Optimal Storage Temperature and Matrix Before Analyzing Mycophenolic Acid

Tracey, Jason MSc*; Brown, Nigel William PhD*; Tredger, J. Michael PhD, FRCPath*,†

doi: 10.1097/FTD.0b013e31824c2d50
Original Article

Background The immunosuppressant mycophenolic acid (MPA) is widely used in solid organ transplantation and increasingly in hematological conditions and autoimmune disease. Concentration monitoring is generally restricted to specialist laboratories associated with transplant centers to which samples are referred, and delays in transit may occur both from the patient to the local laboratory and from there to the specialist laboratory. The instability of the mycophenolate glucuronides in plasma is well described, but the data on MPA stability in patient samples are limited, particularly in whole blood. This study was designed to assess the stability of MPA in patient samples and to establish the correct sample type and optimal transport conditions for therapeutic drug monitoring.

Methods Whole-blood samples received in the laboratory for MPA estimation within 2 hours of phlebotomy were aliquoted, separated, and stored at a range of temperatures designed to mimic the range of transit times and conditions seen in this laboratory. Ten whole-blood samples were stored for a maximum of 4 weeks at 4°C, 21°C, or 35°C and plasma at −20°C, 4°C, 21°C, and 35°C. MPA concentrations were measured by liquid chromatography–tandem mass spectrometry.

Results In whole blood at 35°C, there was a significant increase (P = 0.004) in median MPA concentration over time, but concentrations decreased in some samples. At 21°C and 4°C, there were more modest increases (P = 0.04 and 0.02). In plasma at 35°C, there was a significant increase from day 3 to day 28, then a decrease to day 96 in measured MPA concentration. At 21°C, there was a progressive increase in concentration from 7 to 96 days of storage (P < 0.0001). At 4°C and −20°C, plasma samples were stable for 28 days after collection, but at −20°C, there was a subsequent median increase in concentration of 15.2% at day 96.

Conclusions Samples should be separated as soon as practicable after collection and stored at −20°C or 4°C before transport to the analytical laboratory using subambient temperatures if possible.

*IDM Service, Institute of Liver Studies, King's College Hospital

King's College London School of Medicine, London, United Kingdom.

N.W.B. is currently with Clinical Chemistry, Wansbeck General Hospital, Ashington, Northumberland, United Kingdom.

J. Tracey died during the preparation of this article to whose memory this is dedicated.

The authors declare no conflict of interest.

Correspondence: Nigel William Brown, PhD, Clinical Chemistry, Wansbeck General Hospital, Ashington, Northumberland NE63 9JJ, United Kingdom (e-mail:

Received December 1, 2011

Accepted January 20, 2012

© 2012 Lippincott Williams & Wilkins, Inc.