Liquid Chromatography Coupled to Isotope Ratio Mass Spectrometry Expanded to Include Organic Mobile Phases

Abstract

Current commercially available liquid chromatography coupled to isotope ratio mass spectrometry systems (LC-IRMS) oxidize all eluent and thus can only operate with all-aqueous mobile phases, limiting their application to a small subset of analytes and mixtures that can be separated without organic solvents. We report a novel rotating-catalytic disc desolvation device with subsequent laser-activated photocatalytic analyte combustion to create CO 2 for high precision carbon isotope ratio measurements compatible with both aqueous and organic liquid mobile phases. Sucrose, glucose, androsterone, or androsterone acetate in 20% and 50% H 2 O− CH 3 OH solutions were introduced by flow injection to the interface to IRMS for sugars and steroids, respectively. Sucrose δ 13 C VPDB linearity was excellent over 1−10 μg (33−655 nmol C) injections, using IRMS compatible He/1%O 2 oxidation gas. The limit of precise isotope analysis (LOIA) of δ 13 C VPDB was 1 μg (35 nmol C) for sucrose and 10 μg (655 nmol C) for androsterone with average precisions of SD(δ 13 C) ± 0.8‰. Calibration was performed with and bracketed the δ 13 C VPDB isotope ratio range using androsterone-acetate and glucose. With further development to improve sensitivity and application to chromatography, the prototype proof-of-principle LC-IRMS shows promise to resolve a major drawback in current LC-IRMS systems and may open LC-IRMS to many more compounds than currently possible.