The detection of human-derived metabolites as potential diagnostic biomarkers of genetic disorders, metabolic diseases, systemic diseases, and infectious diseases has been much studied in recent years, especially as technical capabilities improve, and statistical procedures are increasingly able to tease critical chemical attributes from complex data sets. Given the complex distribution of human biological matrices, the characterization and/or identification of these chemical entities is technically challenging, and is often confounded by incomplete chromatographic resolution or insufficient discriminatory power of the mass spectrometry (MS) domain. Recently, comprehensive two-dimensional gas chromatography (GC×GC) has evolved into a mature higher separation order technique that offers unprecedented resolving power, which in turn can greatly advantage clinical metabolomics studies via the expansion of metabolite coverage. In this contribution, the current state of knowledge in the development of GC×GC coupled to MS as a high-resolution bioanalytical technique for the analysis of clinical metabolites is reviewed. Selected recent applications (years 2012 to 2021) that emphasize improved GC×GC-MS strategies for clinical human metabolites’ detection, identification, and quantitative analysis are described. In addition, we share our perspectives on current challenges and potential future directions of GC×GC in clinical applications.

中文翻译：

---

具有质谱的综合二维气相色谱：临床代谢组学研究的先进生物分析技术

近年来，人类衍生代谢物的检测作为遗传疾病、代谢疾病、全身性疾病和传染病的潜在诊断生物标志物得到了广泛的研究，特别是随着技术能力的提高，以及统计程序越来越能够从复杂的数据集。鉴于人类生物基质的复杂分布，这些化学实体的表征和/或鉴定在技术上具有挑战性，并且经常被不完整的色谱分辨率或质谱 (MS) 域的鉴别能力不足所混淆。近年来，综合二维气相色谱（GC×GC）已发展成为一种成熟的高分离级技术，提供前所未有的分离能力，通过扩大代谢物覆盖范围。在这篇文章中，回顾了开发 GC×GC 与 MS 作为一种用于临床代谢物分析的高分辨率生物分析技术的当前知识状态。描述了一些近期的应用（2012 年至 2021 年），这些应用强调了改进的 GC×GC-MS 策略，用于临床人体代谢物的检测、鉴定和定量分析。此外，我们分享了我们对 GC×GC 在临床应用中当前面临的挑战和潜在的未来方向的看法。