Stability of heroin, 6-monoacetylmorphine, and morphine in biological samples and validation of an LC-MS assay for delayed analyses of pharmacokinetic samples in rats.
Stability of heroin, 6-monoacetylmorphine, and morphine in biological samples and validation of an LC-MS assay for delayed analyses of pharmacokinetic samples in rats.
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DOI：
10.1016/j.jpba.2012.10.033
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发表时间：
2013-02-23
影响因子：
3.4
通讯作者：
Birnbaum, Angela K.
中科院分区：
文献类型：
--
作者：
Jones, Jessica M.;Raleigh, Michael D.;Pentel, Paul R.;Harmon, Theresa M.;Keyler, Daniel E.;Remmel, Rory P.;Birnbaum, Angela K.
在体内和体外，海洛因迅速降解为6-单乙酰吗啡（6-MAM）和吗啡。海洛因和6-MAM的降解率取决于生物样品的类型、储存时间和条件。为了优化用于大鼠药代动力学研究的样品中海洛因及其代谢物的测定条件，我们研究了海洛因、6-MAM和吗啡在四种生物基质（大鼠血液、大鼠脑匀浆、牛血清和人血浆）中不同条件下的降解时间。用LC-MS测定分析物浓度。目的是确定在安排样本收集和分析方面具有最大灵活性的条件，并获得更多关于血液和组织样本中海洛因稳定性的信息。采用低温溶剂、氟化钠（NaF）和低pH（3.0）的固相萃取法保持样品的稳定性。质量控制在目标值的94.0-105%以内。在海洛因5-200 ng/mL、6-MAM 5-1000 ng/mL和吗啡10-200 ng/mL范围内，所有分析物的变异性为4.0-8.9%。大鼠全血中海洛因对6-MAM的降解速度快于血浆，血浆中海洛因对6-MAM的降解速度快于脑匀浆。在整个加工过程中保持NaF在4 mg/mL，增强了稳定性；全血中NaF浓度升高会导致溶血。经固相萃取处理后的样品在80℃条件下以干燥颗粒的形式保存是海洛因最稳定的环境，优于提取前后的溶液保存。然而，在这些条件下，大鼠血浆中提取后的海洛因和6-MAM水平在一周内下降了6.7-8.3%，在牛血清或人血浆中下降了< 1-4.7%。
Degradation of heroin to 6-monoacetylmorphine (6-MAM) and then morphine happens rapidly in vivo and in vitro. The rates of heroin and 6-MAM degradation depend on the type of biological samples, and the duration and conditions of storage. In order to optimize conditions for measuring heroin and its metabolites in samples collected for pharmacokinetic studies in rats, we investigated the time course of degradation of heroin, 6-MAM, and morphine in four biological matrices: rat blood, rat brain homogenate, bovine serum, and human plasma under various conditions. Analyte concentrations were measured by LC-MS. The goal was to identify conditions that allow maximum flexibility in scheduling sample collection and analysis, as well as gain more information on the stability of heroin in blood and tissue samples. A solid-phase extraction method with ice-cold solvents, sodium fluoride (NaF) and a low pH (3.0) maintained sample stability. Quality controls were within 94.0–105% of the target value. Variability was 4.0–8.9% for all analytes within the range of 5–200 ng/mL for heroin, 5–1000 ng/mL for 6-MAM, and 10–200 ng/mL for morphine. Heroin degradation to 6-MAM was faster in rat whole blood than in plasma, and faster in rat plasma than in rat brain homogenate. Maintaining NaF at 4 mg/mL throughout processing enhanced stability; higher NaF concentrations added to whole blood caused hemolysis. Samples processed through solid phase extraction and stored as dried pellets at 80°C constituted the most stable environment for heroin, and was superior to the storing of samples in solution prior to or after extraction. Nevertheless, post-extraction heroin and 6-MAM levels declined by 6.7–8.3% over one week in rat plasma under these conditions, and by <1–4.7% in bovine serum or human plasma.
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影响因子：
6.7
作者：
WELCH, RM;BROWN, A;DAHL, R
通讯作者：
DAHL, R
影响因子：
3.8
作者：
GARRETT, ER;GURKAN, T
通讯作者：
GURKAN, T
DOI：
10.1016/s0021-9673(00)91213-5
发表时间：
1975-01-01
期刊：
JOURNAL OF CHROMATOGRAPHY
影响因子：
--
作者：
NAKAMURA, GR;THORNTON, JI;NOGUCHI, TT
通讯作者：
NOGUCHI, TT
影响因子：
2.5
作者：
Zuccaro, P;Ricciarello, R;DAscenzo, G
通讯作者：
DAscenzo, G
影响因子：
5.8
作者：
MINAGAWA, T;KOHNO, Y;TSUJI, A
通讯作者：
TSUJI, A