In the past the phrase 'accurate mass' was interpreted very broadly and covered a wide variety of mass spectrometry measurements, with varying precision. Today, most instruments used for accurate mass measurements are capable of achieving precisions of 10 ppm or better. This Guide is concerned with application to small to medium size molecules and resulted from a review of accurate mass applications which was undertaken as part of the VIMMS Programme. The review highlighted the recent rapid growth in the use of mass spectrometry for molecular weight determinations of small to medium sized molecules, particularly in the chemical and biochemical industries. This growth has been fuelled by a number of factors, including the rapid pace of instrument development, enabling accurate mass and molecular weight measurements to be made in a more robust and less costly fashion. A number of experts have expressed concern that this rapid growth has resulted in unreliable data being obtained by operators who often have little experience of AccMass applications or even of mass spectrometry.

Discussion of the issues by experts at a forum meeting highlighted the need to prepare guidance on undertaking key aspects of the methodology in order to obtain robust measurements and traceable data. It was emphasised, however, that preparation of such guidance should be supported by an experimental evaluation of the methodology, including the implications of variations between type of spectrometer. Consequently, an inter-laboratory comparison was organised by LGC as part of the VIMMS programme to evaluate variations in accurate mass measurements and to improve understanding of the key experimental factors in obtaining reliable data from each type of mass spectrometer. The lessons learned from this study have played a major role in shaping the advice offered in the Guide.

The main aim of this document is to provide users and suppliers of AccMass instrumentation with a clear summary of the essential steps in obtaining reliable data. In addition, the reader should obtain a better understanding of the limitations of different types of spectrometer and the particular precautions which are necessary in setting up the instruments and making measurements. We hope that the Guide will also facilitate an understanding of the principles of the technique and prove useful for both private study and training courses. A glossary of the terms used in this Guide has been included to assist in its use for training purposes.