Substantial differences in serum concentrations of psychoactive drugs measured in samples stored for two days or more on standard serum tubes versus serum tubes containing gel separators.

BACKGROUND: Drugs may potentially adsorb to blood collection tubes containing gel separators in the pre-analytical phase of therapeutic drug monitoring (TDM). The aim of this study was to compare measured concentrations of 28 psychoactive drugs and 13 metabolites in spiked serum samples stored on standard (plain) tubes vs. barrier gel tubes during a 2-6 days period at room temperature.

METHODS: Drug-free ("blank") serum samples spiked with mixes of antidepressants, antipsychotics or mood stabilizers (valproic acid and lamotrigine), including relevant metabolites, were transferred to tubes with and without gel, i.e. BD Vacutainer SSTII Advance gel tubes and BD Vacutainer Glass Serum Tubes (Becton-Dickinson Company, Plymouth, UK). Mean serum concentrations of the drugs or metabolites measured by UHPLC-MS/MS analyses of protein-precipitated samples were compared after storage on plain or gel tubes at three time points (day 0, day 2/48 h and day 6/144 h) in room temperature.

RESULTS: Mean serum concentrations of all antidepressants, except for one metabolite, and 13 out of 18 antipsychotic drugs were significantly lower in gel tubes compared to plain tubes after 2 days of storage (2-28 % lower, P<0.05). After 6 days of storage, mean serum concentrations of all antipsychotic drugs and antidepressants were significantly lower in gel tubes vs. plain tubes (9-49 % lower, P<0.02)), except for amisulpride and O-desmethylvenlafaxine. Serum concentrations of the mood stabilizers were not significantly different in gel tubes compared to plain tubes (P>0.1). There was a clear relationship between log P (partition coefficient) and residual serum concentrations during gel tube storage (r -0.50 and -0.42 at day 2 and day 6, respectively; P<0.02).

CONCLUSION: The present study shows that storage on gel for more than 2 days significantly decrease the serum concentrations of antidepressant and antipsychotic drugs as compared with storage in plain tubes. Thus, using tubes with gel separators in the TDM of psychoactive drugs should be reconsidered.