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人血浆和培养的大鼠肝细胞中博来霉素的高效液相色谱测定法。

High-performance liquid chromatography assay of bleomycin in human plasma and rat hepatocytes in culture.

作者信息

Mahdadi R, Kenani A, Pommery N, Pommery J, Hénichart J P, Lhermitte M

机构信息

Laboratoire de Toxicologie, Faculté de Pharmacie de Lille II, France.

出版信息

Cancer Chemother Pharmacol. 1991;28(1):22-6. doi: 10.1007/BF00684951.

DOI:10.1007/BF00684951
PMID:1710176
Abstract

A sensitive and rapid linear-gradient, ion-paired, reversed-phase high-performance liquid chromatography technique using fluorescence detection was developed to quantify bleomycin (BLM) metabolites in the plasma of patients undergoing BLM therapy and in rat hepatocytes that had previously been incubated with 5 x 10(-5) M BLM. We could detect about 70 ng/ml using this procedure. BLM metabolites were assayed in the supernatant fractions of precipitated human plasma and in pellets of rat hepatocytes. Metabolite concentrations were below the level of detection in human plasma samples. In hepatocyte pellets, metabolites such as deamido-BLM A2 and deamido-BLM B2 were detected, indicating that isolated rat hepatocytes in culture can metabolize BLM analogues to the corresponding deamido-BLMs. The high-performance liquid chromatography procedure developed during this work can be used to study the metabolism of BLM in cell culture systems.

摘要

开发了一种灵敏且快速的线性梯度、离子对、反相高效液相色谱技术,采用荧光检测,用于定量接受博来霉素(BLM)治疗患者血浆及先前用5×10⁻⁵ M博来霉素孵育的大鼠肝细胞中博来霉素的代谢产物。使用该方法我们能够检测到约70 ng/ml。在沉淀的人血浆上清液部分和大鼠肝细胞沉淀中测定博来霉素代谢产物。代谢产物浓度在人血浆样本的检测水平以下。在肝细胞沉淀中,检测到脱氨基博来霉素A2和脱氨基博来霉素B2等代谢产物,表明培养的分离大鼠肝细胞可将博来霉素类似物代谢为相应脱氨基博来霉素。在这项工作中开发的高效液相色谱方法可用于研究细胞培养系统中博来霉素的代谢。

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High-performance liquid chromatography assay of bleomycin in human plasma and rat hepatocytes in culture.人血浆和培养的大鼠肝细胞中博来霉素的高效液相色谱测定法。
Cancer Chemother Pharmacol. 1991;28(1):22-6. doi: 10.1007/BF00684951.
2
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本文引用的文献

1
Subcellular fractionation of isolated rat hepatocytes. A comparison with liver homogenate.分离的大鼠肝细胞的亚细胞分级分离。与肝匀浆的比较。
Biochim Biophys Acta. 1980 Nov 3;632(4):619-29. doi: 10.1016/0304-4165(80)90338-4.
2
Interference of chemicals with glycogen metabolism in isolated hepatocytes.
Toxicology. 1980;18(3):213-23. doi: 10.1016/0300-483x(80)90066-9.
3
Reversed-phase paired-ion high-performance liquid chromatographic method for the separation and quantification of multiple bleomycin congeners.反相离子对高效液相色谱法分离和定量多种博来霉素同系物。
J Chromatogr. 1984 Oct 12;310(2):361-71. doi: 10.1016/0378-4347(84)80101-2.
4
Bleomycin hydrolase activity in pulmonary cells.肺细胞中的博来霉素水解酶活性。
J Pharmacol Exp Ther. 1984 Dec;231(3):583-8.
5
Lack of metabolism as the biochemical basis of bleomycin-induced pulmonary toxicity.缺乏代谢作为博来霉素诱导的肺毒性的生化基础。
Proc Natl Acad Sci U S A. 1983 May;80(10):3064-8. doi: 10.1073/pnas.80.10.3064.
6
Bleomycin disposition in children with cancer.博来霉素在患癌儿童体内的处置情况。
Clin Pharmacol Ther. 1983 May;33(5):668-73. doi: 10.1038/clpt.1983.91.
7
Bleomycin hydrolase activity and cytotoxicity in human tumors.人肿瘤中的博来霉素水解酶活性与细胞毒性。
Cancer Res. 1982 Oct;42(10):4026-31.
8
High-performance liquid chromatographic determination of components of bleomycin preparations.高效液相色谱法测定博来霉素制剂的成分
J Pharm Sci. 1981 Aug;70(8):878-80. doi: 10.1002/jps.2600700811.
9
Bleomycin-resistant cells contain increased bleomycin-hydrolase activities.博来霉素耐药细胞中博来霉素水解酶活性增强。
Biochem Biophys Res Commun. 1981 Jul 16;101(1):55-60. doi: 10.1016/s0006-291x(81)80009-5.
10
Isolation and preliminary characterization of bleomycin-resistant mutants from Chinese hamster ovary cells.
J Cell Physiol. 1981 Apr;107(1):147-53. doi: 10.1002/jcp.1041070116.