Accurate mass analysis at high resolution can be used to determine elemental compositions and is often essential for conclusive metabolite identification. Reference standards can play an important role in the success of the analysis. We have discovered that perfluorinated acid anhydride/fluorinated alkylalcohol (PF-anh/F-alc) derivatives of glyphosate and aminomethylphosphonic acid are sensitively analysed by negative-ion electrospray ionization (ESI) and by positive-ion chemical ionization (CI). Based upon these results, PF-anh/F-alc derivatives of amino acids and PF-anh derivatives of primary amines were prepared, greatly expanding our collection of reference standards for accurate mass measurements. Sample ions are not suppressed since the reference standards can be selected based upon a narrow mass range of interest. They are volatile and, due to the degree of fluorination, have accurate masses favourably close to nominal mass. They are adequately soluble in reverse phase high-performance liquid chromatography solvents, making them particularly useful for ESI. Several examples of positive-ion CI and negative-ion electrospray MS accurate mass analyses of metabolites, obtained using the PF-anh/F-alc derivatives, are described.