We investigated the change in drug concentrations in serum stored in sterilized vacuum tubes for serum separation. The serum concentrations of seven drugs-phenytoin, phenobarbital, carbamazepine, vancomycin, valproate, theophylline and digoxin-were determined after storage in three different vacuum tubes-Vacutainer® SST and SST II (SST, SST II, Becton Dickinson Co. Ltd.) and Neo-Tube® GP-SP 1029 (GP-SP, Nipro Co.). Though there was no change in the serum drug concentrations for any of the tested drugs in GP-SP, the concentrations of phenytoin, phenobarbital and carbamazepine in the serum stored in SST and SST II were significantly decreased due to adsorption onto the serum separator. The degree of adsorption was greater for the SST tube than the SST II tube and for the drugs, the order of adsorption was phenytoin>carbamazepine>phenobarbital. The adsorption of phenytoin onto the separator of SST depended on several storage conditions, such as initial drug concentration, storage temperature and storage volume, while its adsorption onto the SST II separator depended on storage temperature and storage volume. In addition, the change in phenytoin concentration during storage in the SST tube was well correlated with the free fraction of the drug. This indicates that protein binding is an important factor affecting the stability of drug concentrations in serum stored in separation tubes.
Overall, the results of our study indicate that for accurate therapeutic drug monitoring, it is necessary to select vacuum serum separation tubes on the basis of drug concentration stability data for them.
