Mass spectrometry of domoic acid, a marine neurotoxin

Abstract

Domoic acid is a naturally occurring amino acid, formerly available in iimited amounts as a natural product of some algae of the family Rhodomelaceae. As the result of a recent incidence of toxicity in cultured blue mussels (Mytiius eáulis) from a highly localized region of Atlantic Canada, useful amounts of t h i substance are likely to become available in the near future. Domoic acid is an important substance for fundamental studies in neurobiology as it possesses the highest afinity amongst known substances for the kainate receptors of the central nervous system. The present work describes fast atom bombardment (FAB) m a s spectra of domoic acid, and of some of its isomers present in minor quantities in contaminated mussel extracts. These FAB spectra are subject to interferences from beam-induced reduction reactions associated with matrices such as glycerol, but not with others such as 3-nitrobenzyl alcohol. Tandem mass spectrometry of the MH+ ions from these compounds is also reported. As a more feasible approach to quantitative analysis at trace levels, formation of the volatile tert-butyldimethylsilyl derivatives has been investigated and shown to be highly promising.

High-throughput quantitative analysis of domoic acid directly from mussel tissue using Laser Ablation Electrospray Ionization – tandem mass spectrometry

“…This spectrum is analogous to an ESI-MS spectrum and shows [M þ H] þ and [M þ Na] þ ions as well as minor fragment ions produced in the MS source. Selecting the m/z 312 ion as a precursor in MS/MS yielded a product ion spectrum consistent with that reported in the literature for DA (Thibault et al, 1989) showing multiple sequential losses of H 2 O and CO arising from the multiple carboxylic acid functional groups. Despite the complexity of the mussel tissue matrix, DA detection by LAESI-MS/MS was surprisingly selective and a representative product ion spectrum could also be obtained directly from mussel tissue homogenate (Fig.…”

Validated HPLC-MS/MS Method To Quantify Low Levels of Domoic Acid in Plasma and Urine after Subacute Exposure

“…The enhanced product ion (EPI) mass spectra are shown in Figure . The product ions observed in the MS 2 spectra for DA ([M + H] + m / z 312) are consistent with published spectral data. , The MS 3 spectra of the two product ions of DA ( m / z 312 > 294 and m / z 312 > 266) and THDA ( m / z 316 > 298 and m / z 316 > 270) support the analogous fragmentation of the two compounds. HPLC-MS/MS multiple reaction monitoring (MRM) was optimized for quantification of DA.…”

“…The product ions observed in the MS 2 spectra for DA ([M + H] + m/z 312) are consistent with published spectral data. 31,32 The MS 3. The on-column limit of detection (LOD) of DA was determined to be 0.52 pg (1.7 fmol) (Figure 4A).…”

Domoic Acid

“…(Figure 8.4). One low-mass ion at m/z 74 can be attributed to the ion [CO 2 HÀ ÀCHÀ À À ÀNH2] þ , which is characteristic of protonated amino acids (Thibault et al, 1989). The peaks with red labels in Figure 8.3 correspond to ions in the fragmentation pathway of Figure 8.4.…”