Validated hydrophilic interaction LC-MS/MS method for simultaneous quantification of dacarbazine and 5-amino-4-imidazole-carboxamide in human plasma

文献类型： 外文期刊

第一作者： Yang, Yuhui

作者： Yang, Yuhui;Zhang, Weihua;Liu, Yanhong

作者机构：

关键词： Dacarbazine;5-Amino-4-imidazole-carboxamide;Matrix effect;Carryover;Hydrophilic interaction chromatography;LC-MS/MS;Primary and secondary amine;Pharmacokinetics;METASTATIC MELANOMA;METABOLITE 5-AMINOIMIDAZOLE-4-CARBOXAMIDE;INTERACTION CHROMATOGRAPHY;MASS-SPECTROMETRY;ION SUPPRESSION;PHARMACOKINETICS;EXTRACTION;CHEMOTHERAPY

期刊名称：TALANTA （ 影响因子：6.057； 五年影响因子：5.386 ）

ISSN：

年卷期：

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收录情况： SCI

摘要： A hydrophilic interaction high performance liquid chromatography-tandem mass spectrometric method has been developed and validated for simultaneous quantification of dacarbazine (DTIC) and its terminal metabolite, 5-amino-4-imidazole-carboxamide (AIC) in human plasma. The plasma samples are first extracted by a C8 + SCX mixed-mode 96-well plate to extend the extraction stability of DTIC and AIC. The extracted residues are further cleaned by a primary and secondary amine (PSA) adsorbent for minimization of matrix effect. Analyses are done on an Amide-80 HPLC column coupled to a tandem mass spectrometer fitted with an atmospheric pressure turbo ion spray ionization interface in the positive-ion mode. Both DTIC and AIC have reproducible retention times on the Amide-80 HPLC column. This type of column not only has an excellent column life (over 4000 injections), but also has zero carryover effect. The injection volume should be limited at 10 mu L or less to avoid the peak splitting. The validated concentration ranges are from 0.5 to 500 ng/mL for DTIC and from 2.0 to 500 ng/mL for AIC. The validated method has been successfully applied to determine the pharmacokinetic profiles for human patients receiving DTIC infusions. (C) 2008 Elsevier B.V. All rights reserved.

分类号： O65

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