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评估 30 种抗精神病药物在储存血样中的稳定性。

Assessment of the stability of 30 antipsychotic drugs in stored blood specimens.

机构信息

Victorian Institute of Forensic Medicine, Southbank 3006, Australia.

出版信息

Forensic Sci Int. 2012 Feb 10;215(1-3):152-8. doi: 10.1016/j.forsciint.2011.02.022. Epub 2011 Mar 26.

Abstract

The stability of 30 common antipsychotics (APs) in spiked whole blood was investigated over ten weeks in a preliminary experiment (designated "P experiment"). Pools of blank blood spiked with drugs at two different therapeutic levels were stored at four different temperatures: 20 °C, 4 °C, -20 °C, and -60 °C and extracted once weekly in duplicate, using a previously published method. A loss of >15% of the initial drug concentration was considered to indicate possible instability and the respective drugs were selected for further investigation in a final experiment (designated "F experiment"). Eight APs (chlorpromazine, chlorprothixene, fluspirilene, droperidol, olanzapine, thioridazine, triflupromazine, and ziprasidone) were incorporated into the F experiment. The same conditions were used in both experiments, however only a high therapeutic drug concentration was chosen for the F experiment and the storage time was extended to 20 weeks. All drugs of interest in the F experiment showed significant losses after 20 weeks of storage under at least one storage condition. The most notable results involved olanzapine, where losses of almost 100% in all storage temperatures were observed. Drug degradation in fluspirilene samples was significant after 20 weeks under all storage conditions. Overall, extensive degradation was seen with approximately 80% drug loss when stored at 20 °C and 4 °C with samples also seriously affected by degradation of up to 50% when stored at -20 °C and -60 °C, respectively. Ziprasidone remained stable when stored at 4 °C, -20 °C, and -60 °C over 9 weeks, however significant degradation was observed when stored at 20 °C, with a loss of almost 100% after 20 weeks of storage. The time period and temperature of storage of biological samples can have a significant influence on the stability of several APs. It is therefore important to be aware of potential changes in drug concentrations during storage when interpreting analytical results.

摘要

在初步实验(称为“P 实验”)中,研究了 30 种常见抗精神病药物(APs)在添加药物的全血中的稳定性,为期十周。将含有两种不同治疗水平药物的空白血液样本储存在四个不同温度下:20°C、4°C、-20°C 和-60°C,并每周提取一次,一式两份,使用先前发表的方法。如果初始药物浓度损失超过 15%,则认为可能不稳定,相应的药物将被选择用于最终实验(称为“F 实验”)进一步研究。八种 APs(氯丙嗪、氯普噻吨、氟司匹林、氟哌啶醇、奥氮平、奋乃静、三氟拉嗪和齐拉西酮)被纳入 F 实验。两个实验使用相同的条件,但仅选择 F 实验中的高治疗药物浓度,并将储存时间延长至 20 周。在 F 实验中,所有感兴趣的药物在至少一种储存条件下储存 20 周后都显示出明显的损失。最显著的结果涉及奥氮平,在所有储存温度下,几乎 100%的损失。在所有储存条件下,氟司匹林样品在 20 周后降解明显。总体而言,在 20°C 和 4°C 下储存时,药物降解约 80%,损失约 80%,当在-20°C 和-60°C 下储存时,样品分别受到高达 50%的降解严重影响。齐拉西酮在 4°C、-20°C 和-60°C 下储存 9 周时保持稳定,但在 20°C 下储存时观察到明显降解,在 20 周储存后几乎损失 100%。生物样本的储存时间和温度会对几种 APs 的稳定性产生重大影响。因此,在解释分析结果时,注意储存过程中药物浓度的潜在变化非常重要。

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