The development of robust analytical methods remains one of the most important (and costly) parts of chemical metrology. The separation of targeted constituents from other components in a sample matrix is necessary for accurate and precise measurements. Multidimensional chromatography is an important analytical tool since it provides high chromatographic resolution. The Chemical Sciences Division has used SRMs to thoroughly evaluate the quantitative capabilities of both GCxGC and LCxLC and examine the parameters that impact quantitation such as peak description, integration, data processing and experimental parameters. In addition to the investigation on the quantitative capabilities of two-dimensional chromatography, researchers at NIST have studied the qualitative strengths of the instrumentation, including non-targeted analysis. Non-targeted screening is an emerging analytical technique where previously unknown compounds can be identified through a combination of chromatographic and mass spectra data. Currently, GCxGC and LCxLC methods are being developed for the non-targeted screening of environmental, food, and nutritional supplement samples.