On-Cell Stability of Digoxin, Lithium, Phenytoin, Valproic Acid, and Vancomycin for Therapeutic Drug Monitoring

A common problem in clinical laboratories and outpatient clinics is processing specimens rapidly to comply with specimen stability criteria. Currently, for therapeutic drug monitoring, the laboratory must centrifuge specimens and remove the serum or plasma from cells within 2 hours. Many of these drugs are monitored in the outpatient setting, which may require longer transportation times. This creates challenges for the laboratory in processing samples within 2 hours and may result in unnecessary rejection of otherwise acceptable specimens if blood is left on cells too long. The objective of this study was to determine the effect of storage time before centrifugation on the stability of digoxin, lithium, phenytoin, valproic acid, and vancomycin in blood.

The concentration of 5 therapeutic drugs was examined following extended on-cell storage at room temperature (RT). For each drug studied, 3 red-top, no gel serum tubes per patient were collected and maintained at RT for 0.5, 6, and 12 hours after collection. Statistically significant changes from the 0.5-hour control were determined using repeated-measures ANOVA. Phenytoin studies were supplemented with spiked specimens. The spiked whole blood samples were mixed and left at RT for 0.5, 2, 4, 6, or 12 hours after collection.

The concentration of digoxin, lithium, phenytoin, valproic acid, and vancomycin were all within ±10% of the baseline concentration when left at RT on cells up to 12 hours.

All 5 drugs showed adequate stability in unprocessed clotted blood for up to 12 hours at RT. This data can alleviate constraints on processing samples for therapeutic drug monitoring in the clinical laboratory.