Don Kuehl

Mass spectrometry has become a fundamental tool for compound identification or confirmation by virtue of its ability to obtain elemental composition determination (formula identification) by accurate mass measurements. The speed, sensitivity, and ease of interfacing the technique with gas chromatography and liquid chromatography make it the technique of choice for many applications. However, accurate mass measurements must be made with care, and sometimes they can require careful calibration procedures and validation methods. In addition to accurate mass measurements, the isotope abundance distribution also provides information unique to a given chemical formula. However, the mass spectral accuracy required for accurate isotope modeling has not been easy to obtain previously. More recent approaches (1–3) that calibrate the spectral line-shape show promise in obtaining the necessary level of spectral accuracy but still require careful calibration methods with the use of known standards. This article..

The ability to perform accurate mass measurements in mass spectrometry (MS) for elemental composition determination (ECD, also known as formula identification) provides a powerful tool for assisting in the identification of unknown compounds. Recent advances in data processing methods have demonstrated the ability to obtain mass accuracy in the 5–10 ppm range on routine single- and tandem-quadrupole systems (1,2), sufficient to assist in the formula identification. However, even on more expensive high-resolution systems such as quadrupole time-of-flight (qTOF) or Fourier transform (FT)–MS instruments that are capable of routinely measuring mass accuracy in the 1–3 ppm range, the formula identification is not unique, particularly for higher molecular weight compounds. By calibrating instruments to obtain high spectral accuracy as well as mass accuracy, the ability to unambiguously identify the formula is improved substantially, particularly on low-resolution systems.

The exploding field of proteomics has highlighted the need to improve the performance of mass spectrometry, both quantitatively and qualitatively. These needs have led instrument manufacturers to produce instruments of increasingly higher quality, but little work has been done to address the fundamental errors inherent in the measurement technique itself. This paper examines these errors and demonstrates that the appropriate mathematical correction of MS data can significantly improve the performance of both low- and high-resolution instruments.