Development and validation of a novel LC-MS/MS method for simultaneous determination of abiraterone and its seven steroidal metabolites in human serum: Innovation in separation of diastereoisomers without use of a chiral column.
Development and validation of a novel LC-MS/MS method for simultaneous determination of abiraterone and its seven steroidal metabolites in human serum: Innovation in separation of diastereoisomers without use of a chiral column.
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DOI：
10.1016/j.jsbmb.2016.04.002
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发表时间：
2017-09
影响因子：
4.1
通讯作者：
Sharifi, Nima
中科院分区：
文献类型：
--
作者：
Alyamani, Mohammad;Li, Zhenfei;Upadhyay, Sunil K.;Anderson, David J.;Auchus, Richard J.;Sharifi, Nima
醋酸阿比特龙（AA）是阿比特龙的前药，被fda批准用于治疗去势抵抗性前列腺癌。阿比特龙在患者体内代谢为更有效的类似物D4A。然而，我们最近报道了这种类似物在AA治疗的患者中进一步代谢为其他代谢物。本研究采用AB Sciex Qtrap 5500质谱分析仪和岛津Nexera UPLC工作站，建立了一种液相色谱-串联质谱法，用于分离和检测人血清中的阿比特龙及其七种代谢物。采用液-液萃取法从人血清中提取分析物和内标物（阿比特龙-d4）。色谱柱为Zorbax Eclipse Plus C18 150 × 2.1 mm, 3.5 μm，柱温为40℃，流动相为35% a（0.1%甲酸水溶液），65% B（0.1%甲酸甲醇：乙腈；60:40）。电喷雾电离采用正模式，多反应监测，总运行时间为13 min。阿比特龙在2 ~ 400 ng/mL范围内呈线性，所有代谢物在0.1 ~ 20 ng/mL范围内呈线性。该方法按照美国FDA生物分析方法验证指南进行验证，所有代谢物结果均在可接受范围内。尽管代谢产物之间的结构和质量转变相似，但经过验证的方法分离了所有代谢物，包括非对映体，从而可以准确地鉴定和定量每种化合物。
Abiraterone acetate (AA), the prodrug of abiraterone, is FDA-approved for the treatment of castration-resistant prostate cancer. Abiraterone is metabolized in patients to a more potent analogue, D4A. However, we have recently reported that this analogue is further metabolized to additional metabolites in patients treated with AA. Here, we present a liquid chromatography-tandem mass spectrometry method developed to resolve and detect abiraterone and its seven metabolites in human serum using an AB Sciex Qtrap 5500 mass analyzer coupled with a Shimadzu Nexera UPLC station. Analytes and the internal standard (abiraterone-d4) were extracted from human serum using the liquid–liquid extraction procedure. The analytes were separated using a Zorbax Eclipse Plus C18 150 × 2.1 mm, 3.5 μm column at 40 °C and an isocratic mobile phase 35% A (0.1% formic acid in water), 65% B (0.1% formic acid in methanol: acetonitrile; 60:40). Electrospray ionization in positive mode was applied with multiple reaction monitoring in a total run time of 13 min. Abiraterone detection was linear in the range 2–400 ng/mL and all metabolites from 0.1–20 ng/mL. The method was validated following US FDA guidelines for bioanalytical method validation, and all the metabolite results were within the acceptance limits. Despite the similarity in structure and mass transition between the metabolites, the validated method separated all the metabolites, including diastereomers, to allow accurate identification and quantitation of each compound.
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影响因子：
28.2
作者：
Miyamoto DT;Lee RJ;Stott SL;Ting DT;Wittner BS;Ulman M;Smas ME;Lord JB;Brannigan BW;Trautwein J;Bander NH;Wu CL;Sequist LV;Smith MR;Ramaswamy S;Toner M;Maheswaran S;Haber DA
通讯作者：
Haber DA
影响因子：
64.8
作者：
Li Z;Bishop AC;Alyamani M;Garcia JA;Dreicer R;Bunch D;Liu J;Upadhyay SK;Auchus RJ;Sharifi N
通讯作者：
Sharifi N
DOI：
10.1016/j.urolonc.2015.03.021
发表时间：
2015-06-01
影响因子：
2.7
作者：
Grist, Emily;Attard, Gerhardt
通讯作者：
Attard, Gerhardt
影响因子：
11.5
作者：
Kluetz, Paul G.;Ning, Yang-Min;Pazdur, Richard
通讯作者：
Pazdur, Richard
DOI：
10.1056/nejmoa1209096
发表时间：
2013-01-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Ryan CJ;Smith MR;de Bono JS;Molina A;Logothetis CJ;de Souza P;Fizazi K;Mainwaring P;Piulats JM;Ng S;Carles J;Mulders PF;Basch E;Small EJ;Saad F;Schrijvers D;Van Poppel H;Mukherjee SD;Suttmann H;Gerritsen WR;Flaig TW;George DJ;Yu EY;Efstathiou E;Pantuck A;Winquist E;Higano CS;Taplin ME;Park Y;Kheoh T;Griffin T;Scher HI;Rathkopf DE;COU-AA-302 Investigators
通讯作者：
COU-AA-302 Investigators