ABSORPTION OF THERAPEUTIC DRUGS BY BARRIER GELS IN SERUM SEPARATOR BLOOD COLLECTION TUBES - VOLUME-DEPENDENT AND TIME-DEPENDENT REDUCTION IN TOTAL AND FREE DRUG CONCENTRATIONS

The stability of seven commonly monitored therapeutic drugs in serum w as examined following storage in Vacutainer SST(TM) and Corvac(TM) ser um separator blood collection tubes. Significant decreases (ranging fr om 5.96 to 64.5%) in the measured concentrations of phenytoin, phenoba rbital, lidocaine, quinidine, and carbamazepine were observed, as a fu nction of both time and sample volume, when serum was stored in Vacuta iner SST serum separator blood collection tubes. In contrast, measured concentrations of theophylline and salicylate did not change under id entical specimen storage conditions. No significant changes in the con centrations of phenytoin, phenobarbital, carbamazepine, theophylline, quinidine, and salicylate were observed when serum was stored in Corva c serum separator blood collection tubes. Only serum lidocaine concent rations decreased (ranging from 31.5% to 72.6%, depending on sample vo lume) after storage in Corvac tubes for 24 hours. The apparent decreas es in serum concentrations of therapeutic drugs in both Vacutainer SST and Corvac tubes were most pronounced when small volumes (200-500 mu L) of serum remained in contact with the barrier gels for prolonged pe riods of time (> 2-6 hours). These decreases were due to absorption of drugs by the barrier gels, as demonstrated by the recovery of drugs f ollowing chemical extraction of the barrier gels with methanol. For ph enytoin and phenobarbital, the reduction in total drug concentrations also resulted in a proportional decrease in free drug concentrations a nd was dependent on the extent of protein binding by the drug. None of the therapeutic drugs used in this study were adversely affected by p rolonged storage in standard red top Vacutainer blood collection tubes without barrier gels. The data suggest that serum separator blood col lection tubes should be used with extreme caution for therapeutic drug monitoring, particularly when reduced sample volumes or prolonged spe cimen storage may be required.