Ascorbic Acid Improves the Stability of Buprenorphine in Frozen Whole Blood Samples

Buprenorphine (BUP) was not long-term stable in whole blood samples preserved with fluoride citrate (FC) and fluoride oxalate (FX) mixtures when stored at -20°C. On average, only half of the initial concentrations of BUP was recovered after 12 weeks of storage at -20°C when interrupted by 3-4 thaw/freeze cycles. Norbuprenorphine (NBUP) was less unstable; approximately 90% was recovered after 12 weeks of storage at -20°C. The instability was less at 5°C, but the formation of BUP and NBUP from their glucuronides was observed at that temperature, especially in FC-preserved blood. The substances were stable for at least 5 months when stored uninterrupted at -80°C. The instability of BUP and NBUP in FC- and FX-preserved whole blood stored at -20°C was eliminated when the samples were modified with 30 mM ascorbic acid (ASC) prior to storage. The mean recoveries were greater than 95% after a 5-month interrupted storage period at -20°C when modified with ASC.