Mass spectrometry (MS) interfaced with liquid chromatography (LC) was once considered a technology that was reserved for rather specific applications that appeared to work in sequence with the phases of the moon. Early adventures with thermospray and particle beam interfaces proved to be of limited use, and it was not until atmospheric pressure ionization established itself that we could regard LC–MS as the analytical tool of choice for a considerable range of challenges. Indeed, advances in source design and increased ion transmission have presented a new generation of instruments that use hybrid technology such as quadrupole-time of flight (QToF), ToF–ToF and quadrupole ion-trap ToF, which provide even higher levels of confidence as a consequence of higher mass accuracy and enhanced structural information.

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