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.