Study on the stability of antipsychotic drugs in clinical samples within serum collection tubes with and without separating gel.

BACKGROUND

The study evaluated loss due to adsorption of selected antipsychotic drugs in serum samples collected in blood collection tubes with and without separation gel using real clinical specimens.

METHODS

Clinical serum specimens (n = 30 per drug) were obtained from paired blood collection tubes with and without separation gel. After clotting for approximately 2 h at room temperature, samples were centrifuged, and Day 0 drug concentrations were measured by LC-MS/MS within 2 h after centrifugation. To distinguish intrinsic analyte instability from separation-gel-associated loss, serum aliquots from both gel and non-gel tubes were stored in the dark in a monitored refrigerator set at 4°C, with recorded temperatures ranging from 3.6°C to 4.8°C, and reanalyzed on Days 2 and 7.

RESULTS

On Day 0, the concentrations of clozapine and aripiprazole were significantly lower in separation-gel tubes than in non-gel tubes, with mean relative reductions of 7.86% and 5.02%, respectively, although both remained within the predefined ±15% acceptance criterion. In non-gel tubes, clozapine remained stable during refrigerated storage, with residual concentrations of 99.1% on Day 2 and 98.3% on Day 7 relative to Day 0. In contrast, clozapine in gel tubes decreased to 95.0% on Day 2 and 89.6% on Day 7. The gel versus non-gel difference was significant on Day 7, with a mean additional loss of 8.7% in gel tubes compared with non-gel tubes (p < 0.001). Aripiprazole showed a lower concentration in gel tubes on Day 0 but no further time-dependent loss in either tube type during storage. No relevant loss was observed for the remaining antipsychotic drugs and metabolites.

CONCLUSION

Under the tested conditions, most analytes showed no clinically relevant concentration loss during 7 days of refrigerated storage. Clozapine showed a measurable decrease in separation-gel tubes but not in non-gel tubes, suggesting an additional gel-associated contribution that may affect TDM interpretation near clinical decision thresholds. Aripiprazole showed an early tube-related difference without further storage-dependent loss. These findings should be interpreted within the evaluated tube brand, gel formulation, storage condition, and concentration ranges.