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Analysis of the Doxorubicin and Doxorubicinol in the Plasma of Breast Cancer Patients for Monitoring the Toxicity of Doxorubicin.
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-08-25 , DOI: 10.2147/dddt.s251144 Yahdiana Harahap 1 , Puspitasari Ardiningsih 1 , Agatha Corintias Winarti 1 , Denni Joko Purwanto 2
Drug Design, Development and Therapy ( IF 4.8 ) Pub Date : 2020-08-25 , DOI: 10.2147/dddt.s251144 Yahdiana Harahap 1 , Puspitasari Ardiningsih 1 , Agatha Corintias Winarti 1 , Denni Joko Purwanto 2
Affiliation
Introduction: Doxorubicin is an anthracycline antibiotic used as an anticancer agent. Long-term use of this anticancer agent could accumulate its metabolite, doxorubicinol, and cause cardiomyopathy, due to its cardiotoxicity. This cardiotoxic effect depends on the amount of doxorubicin and doxorubicinol accumulated in the body. This study aimed to analyze doxorubicin and doxorubicinol levels in the blood plasma of breast cancer patients.
Methods: Participants of this study were 30 breast cancer patients who had received doxorubicin in their therapy regimen. The samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the Acquity UPLC BEH C18 Waters chromatography column (2.1 x 100 mm : 1.7 μm). Plasma (250 μL) samples were prepared by protein precipitation, using methanol. The mobile phase consisted of 0.1% acetic acid (eluent A) and acetonitrile (eluent B), with gradient elution; the flow rate was 0.15 mL/min and runtime, 7 min.
Results and Discussion: This method was linear in the range of 1– 1000 ng/mL for doxorubicin and 0.5– 500 ng/mL for doxorubicinol. This method was successfully used to analyze doxorubicin and doxorubicinol, simultaneously, using hexamethylphosphoramide as the internal standard, in the plasma of breast cancer patients. Results showed that the measured concentrations of doxorubicin and doxorubicinol ranged between 12.54– 620.01 ng/mL and 1.10– 27.00 ng/mL, respectively. The measured cumulative doses of doxorubicin ranged between 48.76 and 319.01 mg/m2; thus, the risk of cardiomyopathy in the surveyed patients was under 4%, according to literature.
Keywords: analysis, breast cancer, cardiotoxic, doxorubicin, doxorubicinol, partial validation, plasma, LC-MS/MS
中文翻译：
乳腺癌患者血浆中多柔比星和多柔比星醇的分析用于监测多柔比星的毒性。
简介：阿霉素是一种蒽环类抗生素，用作抗癌剂。由于其心脏毒性，长期使用这种抗癌剂可能会积累其代谢物阿霉素，并导致心肌病。这种心脏毒性作用取决于体内积累的多柔比星和多柔比星醇的量。本研究旨在分析乳腺癌患者血浆中阿霉素和阿霉素的水平。
方法：这项研究的参与者是 30 名在其治疗方案中接受了阿霉素的乳腺癌患者。使用超高效液相色谱-串联质谱 (LC-MS/MS) 和 Acquity UPLC BEH C18 Waters 色谱柱 (2.1 x 100 mm: 1.7 μm) 对样品进行分析。使用甲醇通过蛋白质沉淀制备血浆 (250 μL) 样品。流动相由0.1%乙酸（洗脱液A）和乙腈（洗脱液B）组成，梯度洗脱；流速为 0.15 mL/min，运行时间为 7 min。
结果与讨论：该方法在多柔比星的线性范围为 1–1000 ng/mL，多柔比星的线性范围为 0.5–500 ng/mL。该方法成功地用于分析乳腺癌患者血浆中的多柔比星和多柔比星醇，同时使用六甲基磷酰胺作为内标。结果表明，阿霉素和阿霉素的测量浓度分别在 12.54–620.01 ng/mL 和 1.10–27.00 ng/mL 之间。测得的阿霉素累积剂量介于 48.76 和 319.01 mg/m 2之间；因此，根据文献，接受调查的患者患心肌病的风险低于 4%。
关键词：分析，乳腺癌，心脏毒性，阿霉素，阿霉素，部分验证，血浆，LC-MS/MS
更新日期：2020-08-25
Methods: Participants of this study were 30 breast cancer patients who had received doxorubicin in their therapy regimen. The samples were analyzed using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), with the Acquity UPLC BEH C18 Waters chromatography column (2.1 x 100 mm : 1.7 μm). Plasma (250 μL) samples were prepared by protein precipitation, using methanol. The mobile phase consisted of 0.1% acetic acid (eluent A) and acetonitrile (eluent B), with gradient elution; the flow rate was 0.15 mL/min and runtime, 7 min.
Results and Discussion: This method was linear in the range of 1– 1000 ng/mL for doxorubicin and 0.5– 500 ng/mL for doxorubicinol. This method was successfully used to analyze doxorubicin and doxorubicinol, simultaneously, using hexamethylphosphoramide as the internal standard, in the plasma of breast cancer patients. Results showed that the measured concentrations of doxorubicin and doxorubicinol ranged between 12.54– 620.01 ng/mL and 1.10– 27.00 ng/mL, respectively. The measured cumulative doses of doxorubicin ranged between 48.76 and 319.01 mg/m2; thus, the risk of cardiomyopathy in the surveyed patients was under 4%, according to literature.
Keywords: analysis, breast cancer, cardiotoxic, doxorubicin, doxorubicinol, partial validation, plasma, LC-MS/MS
中文翻译：
乳腺癌患者血浆中多柔比星和多柔比星醇的分析用于监测多柔比星的毒性。
简介：阿霉素是一种蒽环类抗生素，用作抗癌剂。由于其心脏毒性，长期使用这种抗癌剂可能会积累其代谢物阿霉素，并导致心肌病。这种心脏毒性作用取决于体内积累的多柔比星和多柔比星醇的量。本研究旨在分析乳腺癌患者血浆中阿霉素和阿霉素的水平。
方法：这项研究的参与者是 30 名在其治疗方案中接受了阿霉素的乳腺癌患者。使用超高效液相色谱-串联质谱 (LC-MS/MS) 和 Acquity UPLC BEH C18 Waters 色谱柱 (2.1 x 100 mm: 1.7 μm) 对样品进行分析。使用甲醇通过蛋白质沉淀制备血浆 (250 μL) 样品。流动相由0.1%乙酸（洗脱液A）和乙腈（洗脱液B）组成，梯度洗脱；流速为 0.15 mL/min，运行时间为 7 min。
结果与讨论：该方法在多柔比星的线性范围为 1–1000 ng/mL，多柔比星的线性范围为 0.5–500 ng/mL。该方法成功地用于分析乳腺癌患者血浆中的多柔比星和多柔比星醇，同时使用六甲基磷酰胺作为内标。结果表明，阿霉素和阿霉素的测量浓度分别在 12.54–620.01 ng/mL 和 1.10–27.00 ng/mL 之间。测得的阿霉素累积剂量介于 48.76 和 319.01 mg/m 2之间；因此，根据文献，接受调查的患者患心肌病的风险低于 4%。
关键词：分析，乳腺癌，心脏毒性，阿霉素，阿霉素，部分验证，血浆，LC-MS/MS
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