Standardless, Automated Determination of Chlorine-35 by 35Cl Nuclear Magnetic Resonance Watson, Simon A1; Edwards, Andy J1; Parkinson, John A2 1GlaxoSmithKline Medicines Research Centre, Stevenage, Hertfordshire, UK 2 WestCHEM Department of Pure and Applied Chemistry, University of Strathclyde, Glasgow, UK Corresponding author: Watson, Simon A; GlaxoSmithKline, Gunnelswood Road, Stevenage, Hertfordshire, UK, SG1 2NY; 01438 766685;
[email protected] We present an example of a robust, fully automated, walk-up method to quantify chloride concentration in sample solutions using 35Cl nuclear magnetic resonance (NMR). Minimal user input is required, no standards are acquired at the time of analysis and the submission, acquisition, processing and production of results are seamlessly integrated within existing NMR automation software. The method demonstrated good linearity with R2 = 0.999 over three orders of magnitude of analyte concentration, results that are highly independent of analyte functionality, and the stability of instrument response was such that analyses of additional standards were not required for a period of several months. At a nominal sample concentration of 10 mg/ml in D2O at 400 MHz, a detection limit and a quantitation limit of 0.1 and 0.5% w/w, respectively, was achieved in a 1 hour run time. Robust methodology was achieved by applying a rigorous approach to method development and validation to determine and evaluate fully the time- and sample-dependent factors that affect quantitation in this experiment. 1 Keywords: NMR, 35Cl, chloride, quantitation, walk-up, automation, pharmaceutical analysis Introduction The maxim that “nuclear magnetic resonance (NMR) is inherently quantitative” has become a central dogma of NMR spectroscopy in literature and presentations.