The photobase generator nifedipine as a novel matrix for the detection of polyphenols in matrix-assisted laser desorption/ionization mass spectrometry

Abstract

Matrix assisted laser desorption/ionization mass spectrometry (MALDI-MS) is widely used for the detection and analysis of ionizable compounds. However, the method has less potential for the analysis of neutral compounds, such as polyphenols, owing to their lack of favorable proton-attachment or -removal groups. In this study, we reported for the first time that nifedipine (2,6-dimethyl-3,5-dicarbomethoxy-4-(2-nitrophenyl)-1,4-dihydropyridine), which is a strong photobase generator commonly used in polymerization, can abstract protons from neutral compounds in negative mode-MALDI experiments. When nifedipine (5 mg/ml) was used as a matrix reagent, the limit of detection (LOD) for epigallocatechin-3-O-gallate (EGCG) was determined to be 100 fmol/spot, which constitutes >50-fold improvement compared to the LOD obtained when trans-3-indoleacrylic acid, a matrix reagent previously reported for polyphenol detection, was used. Of the dihydropyridines investigated, only nifedipine facilitated the detection of EGCG, suggesting that the nitrosophenyl pyridine derivative of nifedipine formed by photoreduction under laser irradiation at 355 nm plays a crucial role in detecting polyphenols in negative mode. Reduced MS detection of 5-O-methylnaringenin indicated that nifedipine may preferably remove a proton from the 5-position OH group in the A ring of the flavonoid skeleton. The significant MS detection by nifedipine was extensively observed for polyphenols including flavones, flavonones, chalcones, stilbenoids and phenolic acids. In conclusion, nifedipine can act as a novel matrix for improving polyphenol detection by MALDI-MS in negative mode. Copyright © 2016 John Wiley & Sons, Ltd.

Novel in situ visualisation of rat intestinal absorption of polyphenols via matrix-assisted laser desorption/ionisation mass spectrometry imaging

“…To visualise the in situ absorption behaviour of polyphenols using MALDI-MSI, nifedipine was used as the preferred matrix reagent, together with other common matrix reagents. Our previous studies showed that nifedipine enhanced the ionisation of less-ionisable polyphenols (e.g., flavonols, flavones, flavanones, flavonones, chalcones, stilbenoids, and phenolic acids), by removal of a proton from the polyphenol skeleton due to its photobase properties 20 .…”

Detection and Visualization of Food-derived Polyphenols by Matrix-assisted Laser Desorption/Ionization Mass Spectrometry Imaging

“…(36) However, the MALDI-MS detection of polyphenols, which have neutral chemical structures (except for anthocyanins, which have positively charged flavylium skeletons), has severe limitations owing to their lack of proton removal or addition groups. (37) Moreover, there are several limitations for the aforementioned conventional matrices, such as an abundance of interfering signals in the low-mass range for a positive detection mode and a low ionization efficiency for a negative detection mode. (36) Several attempts at detecting polyphenols by MALDI-MS have been reported in the literature, as listed in Table 1.…”

“…(37) The mechanism of nifedipine-induced MS ionization of polyphenols involves the production of a nitrosophenyl pyridine derivative from nifedipine under laser irradiation at 355 nm. (37) This photobase product plays a crucial role in the deprotonation of polyphenols in negative-mode MALDI-MS [as illustrated in Fig. 2(b)].…”

“…2(b)]. (37) Moreover, the enhanced detection of polyphenols was achieved by the addition of phytic acid, which has been reported as a matrix additive for enhancing the MALDI-MS detection of peptides. (43) According to the nifedipine-aided MALDI-MS analysis of methylated naringenins, the OH group at the 5-position of the flavonoid skeleton A-ring undergoes proton removal by nifedipine.…”

“…(43) According to the nifedipine-aided MALDI-MS analysis of methylated naringenins, the OH group at the 5-position of the flavonoid skeleton A-ring undergoes proton removal by nifedipine. (37) Thus, nifedipine may be useful as a novel and powerful MALDI matrix reagent for the analysis of polyphenols and may contribute to the future application of MALDI-MS imaging for investigating the bioavailability of bioactive polyphenols.…”