Center for Psychopharmacology, Diakonhjemmet Hospital.
Department of Pharmaceutical Biosciences, School of Pharmacy, University of Oslo, Oslo, Norway.
Ther Drug Monit. 2019 Jun;41(3):396-400. doi: 10.1097/FTD.0000000000000592.
Drugs may potentially adsorb to blood collection tubes containing gel separators in the preanalytical phase of therapeutic drug monitoring. 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 versus barrier gel tubes during a 2-6-day period at room temperature.
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, that is, BD Vacutainer SST II Advance gel tubes and BD Vacutainer Glass Serum Tubes (Becton-Dickinson Company, Plymouth, United Kingdom). Mean serum concentrations of the drugs or metabolites measured by ultra-high performance liquid chromatography-tandem mass spectrometry analyses of protein-precipitated samples were compared after storage on plain or gel tubes at 3 time points (day 0, day 2/48 hours, and day 6/144 hours) in room temperature.
Mean serum concentrations of all antidepressants, except for one metabolite, and 13 of 18 antipsychotic drugs were significantly lower in gel tubes compared with 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 versus 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 with 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).
This study shows that storage on gel for more than 2 days significantly decreases the serum concentrations of antidepressant and antipsychotic drugs as compared to storage in plain tubes. Thus, using tubes with gel separators in the therapeutic drug monitoring of psychoactive drugs should be reconsidered.
药物在治疗药物监测的前分析阶段可能会吸附在含有凝胶分离剂的血液采集管中。本研究的目的是比较在室温下 2-6 天内,将加标血清样本储存在标准(普通)管和屏障凝胶管中时,28 种精神药物和 13 种代谢物的测量浓度。
将不含药物的(“空白”)血清样本与抗抑郁药、抗精神病药或心境稳定剂(丙戊酸和拉莫三嗪)的混合物混合,包括相关代谢物,转移到有和没有凝胶的管中,即 BD Vacutainer SST II Advance 凝胶管和 BD Vacutainer Glass Serum Tubes(Becton-Dickinson Company,英国普利茅斯)。使用蛋白质沉淀样品的超高效液相色谱-串联质谱分析测量药物或代谢物的平均血清浓度,并在室温下分别在普通管和凝胶管中储存 3 个时间点(第 0 天、第 2/48 小时和第 6/144 小时)后进行比较。
与普通管相比,在储存 2 天后,所有抗抑郁药(除一种代谢物外)和 18 种抗精神病药中的 13 种的平均血清浓度在凝胶管中明显较低(低 2%-28%,P < 0.05)。储存 6 天后,与普通管相比,所有抗精神病药和抗抑郁药的平均血清浓度在凝胶管中明显较低(低 9%-49%,P < 0.02),除了氨磺必利和 O-去甲文拉法辛。与普通管相比,心境稳定剂在凝胶管中的血清浓度没有明显差异(P > 0.1)。在凝胶管储存期间,血清浓度与 log P(分配系数)之间存在明显的关系(第 2 天和第 6 天分别为 r=-0.50 和 r=-0.42;P < 0.02)。
本研究表明,与储存在普通管中相比,在凝胶中储存超过 2 天会显著降低抗抑郁药和抗精神病药的血清浓度。因此,在对精神药物进行治疗药物监测时,应重新考虑使用带有凝胶分离剂的管。