Related Fragment Screening: Swift and Easy Elucidation of Drug Metabolites

Researchers in the field of drug metabolism take note of a new method for quickly and easily identifying and elucidating the structures of related compounds by LC/MS with related fragment screening and ACD/IntelliXtract.

Related fragment screening takes advantage of the fact that related compounds, such as drug metabolites or degradants, will have some chemical structure similarities to the parent drug. The mass spectra will therefore be similar, as common substructures will yield common fragment ions. Mass spectral relationships can then be used to identify potential metabolites. Furthermore, the relationship between chemical structure and mass spectrum may be used to elucidate the structure of potential metabolites by identifying the sites of modification on the parent drug. Conceptually, this seems simple; however, in practice, interpreting complex LC/MS data can be very challenging.

Software can interpret, label, and organize mass spectral data, making it easier to extract common and related fragment information. Mass spectrum interpretation tools help chemists visualize the relationships between the parent drug and related compounds. ACD/IntelliXtract has the capability to extract chromatographic components, and interpret the pure-component spectrum for each, automatically assigning MH+ or MH- adducts, multimers, and fragment ions. This helps mass spectrometrists quickly glean the relevant information from LC/MS data sets, easing the burden of spectrum interpretation, so that analysts spend less time on routine identification and confirmation, and can focus on solving more challenging problems.

An illustration of how to use ACD/IntelliXtract for related fragment screening in an example of forced degradation was recently presented in a talk at Pittcon 2007 entitled ‘Identification of Impurities Using Liquid Chromatography Hyphenated with Tandem Mass Spectrometry’.

“IntelliXtract can now combine mass spectral identifiers such as 12C, 13C, and MH+, with knowledge of the parent structure, the differences in mass between parent and some unknown, and the inherent shifts in the fragments of these related compounds,” commented Mark Bayliss, Director of Analytical Informatics, ACD/Labs. “This is an important step towards automated structure building from mass spectra. The future is certainly looking to be very exciting in this field.”

More information about related fragment screening can be obtained by downloading the application note Extraction and Elucidation of Metabolites using Related Fragment Screening from the ACD/Labs website. The note illustrates the use of related fragment screening using ACD/IntelliXtract to help identify and determine the structure of metabolites of the antiarrhythmic drug verapamil.

Related fragment screening will be highlighted at an ACD/Labs MS Seminar held in advance of the 55th ASMS Conference on Mass Spectrometry on Sunday, June 3rd, from 1:30–4:30 pm in Indianapolis, IN. View the seminar agenda.

For more information on ACD/IntelliXtract and ACD/MS Manager please visit the article webpage.