Precursor ion scan profiles of acylcarnitines by atmospheric pressure thermal desorption chemical ionization tandem mass spectrometry

Abstract

The fatty acyl esters of L-carnitine (acylcarnitines) are useful biomarkers for the diagnosis of some inborn errors of metabolism analyzed by liquid chromatography/tandem mass spectrometry. In this study the acylcarnitines were analyzed by atmospheric pressure thermal desorption chemical ionization using a commercial tandem mass spectrometer (APTDCI-MS/MS). The method is based on the precursor ion scan mode determination of underivatized acylcarnitines desorbed from samples by a hot desolvation gas flow and ionized by a corona pin discharge. During desorption/ionization step the temperature induces the degradation of acylcarnitines; nevertheless, the common fragment to all acylcarnitines [MH-59](+) is useful for analyzing their profile. APTDCI parameters, including angle of collection and incidence, gas flows and temperatures, were optimized for acylcarnitines. The experiments were performed drying 2 microL of an equimolar mixture of acylcarnitine standards on a glass slide. The specificity was evaluated by comparing product ion spectra and the precursor ion spectra of 85 m/z of acylcarnitines obtained by the APTDCI method and by electrospray ionization flow injection analysis (ESI-FIA). The method was also employed to analyze acylcarnitines extracted from a pathological dried blood spot and a control. The method enables analysis of biological samples and recognition of some acylcarnitines that are diagnostic markers of inherited metabolic diseases. The intrinsic high-throughput analysis of the ambient desorption ionization methods offers a new opportunity either for its potential application in clinical chemistry and for the expanded screening of some inborn errors of metabolism.

Characterization of Rheumatoid Arthritis Subtypes Using Symptom Profiles, Clinical Chemistry and Metabolomics Measurements

“…Thirteen of the top features measured in positive ion mode as well as the acetylcarnitine standard showed the same neutral loss of mass 59.0747 by fragmentation, which is highly indicative of acylcarnitine compounds [35], [36]. The retention times of the features showing this loss was increasing with the mass, indicating higher mass features were less polar.…”

The use of mass spectrometry to analyze dried blood spots

“…A striking observation was the absence in MS spectra of the intact protonated analytes and the presence instead of characteristic fragment ions, which related to thermal degradation in the source. Acylcarnitines, for instance, led to [M + H ‐ 59] + ions that indicated the loss of trimethylamine (Paglia, D'Apolito, & Corso, ). Acylcarnitines were screened with a precursor ion scan that targeted protonated butenoic acid ( m/z 85) as product ion, similar to FIA–ESI–MS/MS analysis (but with the obvious difference that [M + H ‐ 59] + ions were displayed and not [M + H] + ).…”

Enhanced Acylcarnitine Annotation in High-Resolution Mass Spectrometry Data: Fragmentation Analysis for the Classification and Annotation of Acylcarnitines

“…Previous work showed the value of parent and neutral loss monitoring in a quadrupole ion trap for targeted screening of acylcarnitines in biological samples (McClellan et al, 2002 ; Shigematsu et al, 2002 ; Paglia et al, 2008 ; Rinaldo et al, 2008 ). In addition, several studies applied multiple reaction monitoring (MRM) type of approaches using the 85 m / z nominal mass fragment or the neutral loss of 60 to target specifically for acylcarnitines (Maeda et al, 2008 ; Kivilompolo et al, 2013 ; Peng et al, 2013b ) or specific derivatization to probe for acylcarnitines (Minkler et al, 2005 ).…”