10 years of MS instrumental developments--impact on LC-MS/MS in clinical chemistry.

The combination of liquid chromatography and mass spectrometry (LC-MS) is a powerful and indispensable analytical tool that is widely applied in many areas of chemistry, medicine, pharmaceutics and biochemistry. In this review recent MS instrumental developments are presented as part of a special issue covering various aspects of liquid chromatography tandem mass spectrometry (LC-MS/MS) in clinical chemistry. Improvements, new inventions as well as new combinations in ion source technology are described focusing on dual or multimode sources and atmospheric pressure photoionization (APPI). Increasing demands regarding sensitivity, accuracy, resolution and both quantitation and identification guarantee on-going improvements in mass analyzer technology. This paper discusses new hybrid MS instruments that can perform novel scan modes as well as high-resolution mass spectrometers (HRMS) that finally seem to be able to overcome, or at least significantly reduce, their weaknesses in quantitative applications. Ion mobility-mass spectrometry (IMMS) itself is not an invention of the last 10 years, but a lot of progress was made within the last decade that reveals the potential benefits of this combination. This is clearly reflected by the increased number of commercially available instruments and the various designs of IMMS are covered in detail in this review. Selected applications for all these instrumental developments are given focusing on the perspective of clinical chemistry.