Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Louwesweg 6, 1066 EC Amsterdam, The Netherlands.
J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Dec 1;878(31):3199-216. doi: 10.1016/j.jchromb.2010.10.018. Epub 2010 Oct 26.
The heterocyclic aromatic amine, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), has been shown to be carcinogenic in rodents, mice and rats. Following phase I N-hydroxylation and phase II esterification PhIP exerts its carcinogenic effect by binding to DNA purines. Quantitative and qualitative analysis of its bioactivated metabolites as well as it detoxification products is important in studying its biological effects and inter- and intra-individual exposures. A review is presented with an extensive coverage of publications specifically reporting on the analysis of PhIP and its phase I and II metabolites in biological matrices, foodstuff and beverages. Analytical techniques such as liquid and gas chromatography coupled with various detection techniques (mass spectrometry, ultraviolet or fluorescence detection) were mostly applied. We conclude that since the initial identification of PhIP in 1986 a large set of assays has been developed for the analysis of PhIP and its phase I and phase II metabolites in a wide range of matrices, these included food products and biological samples such as plasma, urine and faeces. In addition, it was shown that numerous metabolites were recovered and identified. Thus, we conclude that liquid chromatography coupled to mass spectrometry is clearly the method of choice for sensitive qualitative as well as quantitative analysis with high selectivity and reaching lower quantification levels in the sub pg/mL range. The main aim of this review is that it can be used by other researchers as a resource for method development and optimization of analytical methods of PhIP and its carcinogenic or detoxification products.
杂环芳香胺 2-氨基-1-甲基-6-苯基咪唑[4,5-b]吡啶(PhIP)已被证明在啮齿动物、小鼠和大鼠中具有致癌性。在经历 I 相 N-羟化和 II 相酯化作用后,PhIP 通过与 DNA 嘌呤结合发挥其致癌作用。对其生物活化代谢物及其解毒产物进行定量和定性分析,对于研究其生物学效应和个体内、个体间暴露情况非常重要。本文综述了专门报道生物基质、食品和饮料中 PhIP 及其 I 相和 II 相代谢物分析的出版物,涵盖广泛。液相和气相色谱与各种检测技术(质谱、紫外或荧光检测)相结合的分析技术大多得到了应用。我们得出结论,自 1986 年首次鉴定出 PhIP 以来,已经开发出大量用于分析 PhIP 及其 I 相和 II 相代谢物的方法,这些方法包括食品产品和生物样品,如血浆、尿液和粪便。此外,还回收并鉴定了许多代谢物。因此,我们得出结论,液相色谱-质谱联用显然是一种具有高选择性、可达到亚 pg/mL 范围的低定量下限的灵敏定性和定量分析的首选方法。本文综述的主要目的是为其他研究人员提供一个资源,用于 PhIP 及其致癌或解毒产物的方法开发和优化。