Since nh-PHIP requires an alcohol (typically methanol) as the main solvent, commonly used water-based buffering agents (i.e. phosphate buffer) are unsuitable. The known nh-PHIP compatible piperidine/piperidinium hydrochloride buffer (pKa in methanol 11.22), but it was not compatible with [(IMes)(H)2(mtz)3] + . The piperidine was found to partially displace the mtz co-substrate in the active complex (Scheme 1) and form a detectable complex with iridium (see SI Figure ). Therefore, the more sterically hindered triethylamine/triethylamine hydrochloride buffer (pKa in methanol 10.29) was tested as an alternative (See SI Figure ). No buffer complexation was observed and the nicotinamide hydride signals in the sample were even slightly more intense compared to piperidine buffer (SI, Figure ).