Absorption of Therapeutic Drugs by Barrier Gels in Serum Separator Blood Collection Tubes:Volume- and Time-dependent Reduction in Total and Free Drug Concentrationsa

Abstract

The stability of seven commonly monitored therapeutic drugs in serum was examined following storage in Vacutainer SST and Corvac serum separator blood collection tubes. Significant decreases (ranging from 5.9% to 64.5%) in the measured concentrations of phenytoin, phenobarbital, lidocaine, quinidine, and carbamazepine were observed, as a function of both time and sample volume, when serum was stored in Vacutainer SST serum separator blood collection tubes. In contrast, measured concentrations of theophylline and salicylate did not change under identical specimen storage conditions. No significant changes in the concentrations of phenytoin, phenobarbital, carbamazepine, theophylline, quinidine, and salicylate were observed when serum was stored in Corvac serum separator blood collection tubes. Only serum lidocaine concentrations decreased (ranging from 31.5% to 72.6%, depending on sample volume) after storage in Corvac tubes for 24 hours. The apparent decreases in serum concentrations of therapeutic drugs in both Vacutainer SST and Corvac tubes were most pronounced when small volumes (200-500 microL) of serum remained in contact with the barrier gels for prolonged periods of time (> 2-6 hours). These decreases were due to absorption of drugs by the barrier gels, as demonstrated by the recovery of drugs following chemical extraction of the barrier gels with methanol. For phenytoin and phenobarbital, the reduction in total drug concentrations also resulted in a proportional decrease in free drug concentrations and was dependent on the extent of protein binding by the drug. None of the therapeutic drugs used in this study were adversely affected by prolonged storage in standard red top Vacutainer blood collection tubes without barrier gels. The data suggest that serum separator blood collection tubes should be used with extreme caution for therapeutic drug monitoring, particularly when reduced sample volumes or prolonged specimen storage may be required.

Preanalytical quality improvement: in quality we trust

“…Separator gels are also a common component of blood collection tubes, and they serve as a barrier between serum and clot or plasma and cells, respectively, after centrifugation of tubes. A well-recognized drawback of serum/plasma separator tubes is the potential for the separator gel to absorb hydrophobic compounds such as some drugs [29] . Another problem is that the gel itself is unstable under extreme temperature conditions and can produce an oily film in serum/plasma, which in turn can obstruct instrument probes with subsequent downtime.…”

Comparison of Improvacuter™ tubes with BD Vacutainer™ tubes for various hormones in the aspects of stability and influence of gel separators

“…In many studies the decline Brought to you by | University of Louisville Authenticated Download Date | 2/4/15 10:33 AM Lower RL, the lower range limit calculated from the CV A (%) of the results obtained from the reference tube (A) at 0 h; Upper RL, the upper range limit of the CV A (%) of the results obtained from the reference tube (A) at 0 h. a Results excceding the reference lower or upper range limits A: 5 mL secondary tube containing the serum transferred from without gel BD Vacutainer Clot Activator tube just after centrifugation, B: 8 mL Improvacuter Gel and Clot Activator tube, C: 8.5 mL BD Vacutainer SST II Advance tube, D: 10 mL Improvacuter tube. in the therapeutic drug levels was associated with their absorbtion by gel [11,12]. Morovat In our study the data obtained from statistical analyses (two-tailed paired t-test and Wilcoxon's test) at 0 h were statistically significant for cortisol, estradiol, free T4, testosterone, TSH and LH between BD Vacutainer Clot Activator tube, BD Vacutainer SST II Advance tube and Improvacuter Gel and Clot Activator tube (Table 2).…”

Evaluation of BD Vacutainer SST™ II plus tubes for special proteins testing

“…One limitation was that the gel contained within serum separator tubes had the potential for adsorbing analytes of interest (8,9) or releasing material that may interfere with analytes (10). Another limitation of serum separator tubes was that certain analytes, such as therapeutic drugs and steroid hormones, may be instable when serum were stored on the barrier for long periods of time (2,3). Moreover, the instability of the gel itself and the presence of gel globules or an oily film in the serum were observed under extreme temperature conditions, which may cause probe clogged and then instrument down time.…”

“…This type of tubes contained a gel barrier that moved to the cell/serum interface during centrifugation based on a density gradient and formed an impermeable barrier between the serum and the clot, and then facilitated rapid separation of serum from cellular constituents of blood and also prevented hemolysis upon prolonged storage. However, some limitations associated with gel tubes had been observed, for example, gel and analyte stability (2,3). In order to circumvent these problems, BD released a new serum separator tube containing a new gel (BD Vacutainer s SST TM II Plus (BD SST TM II Plus)) which was superior to the existing gel (4).…”