23


sensitivity, peak shape, baseline artefact and retention perspective, none of the alternative high pH mobile phases tested offered better properties to ammonium hydroxide for MS friendly SIM development work.


Conclusions Excellent correlation of analyte retention when transferring from organic mobile phase additives to phosphate buffers at low and mid- pH was observed. In most cases absolute elution order and resolution was maintained while significantly increased UV sensitivity and decreased baseline slope were observed with phosphate buffers.


Data from this comparison suggests that many SIMs (or other methods) could be developed from an MS compatible method and transferred directly to an appropriate phosphate method for increased UV sensitivity and method robustness. Alternatively, a phosphate method could be directly transferred to an MS friendly alternative for identification of unknowns with a high degree of confidence.


In the few cases where a change in selectivity is observed and resolution decreases dramatically, it is suggested that experimental modelling is investigated (e.g.utilising Drylab or ACDLabs LC Simulator) to re-optimise the separation. This may involve varying gradient slope or


temperature or a combination of both to achieve the separation.


In the high pH mobile phase investigation, no alternative additive provided similar properties to the ammonium hydroxide generic method. Low retention correlation, increased baseline artefacts, poorer peak shapes and lower analyte sensitivity were typically observed with the majority of the alternative mobile phases. Alternative approaches to clean ammonium hydroxide mobile phases in order to decrease the artefact level are therefore required e.g. through use of appropriate mobile phase filters.


Acknowledgements


The authors would like to thank Adrian Davis (Research Analytics, Pfizer Global Research & Development, Sandwich) for useful discussions regarding ionic strength determination.


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