Synthesis of benzofurazan derivatization reagents for carboxylic acids in liquid chromatography/electrospray ionization–tandem mass spectrometry

Abstract

The applicability of benzofurazan derivatization regents to carboxylic acids analysis in LC/ESI-MS/MS (high-performance liquid chromatography/electrospray ionization tandem mass spectrometry) was examined. The product ion spectra of DAABD-AE {4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole}, DAABD-PZ {4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-N-piperazino-2,1,3-benzoxadiazole}, DAABD-PiCZ {4-[4-carbazoylpiperidin-1-yl]-7-[2-(N,N-dimethylamino)ethylaminosulfonyl]-2,1,3-benzoxadiazole}, DAABD-ProCZ {4-[2-carbazoylpyrrolidin-1-yl]-7-[2-(N,N-dimethylamino) ethylaminosulfonyl]-2,1,3-benzoxadiazole} and DAABD-Apy {4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(3-aminopyrrolidin-1-yl)-2,1,3-benzoxadiazole}, and their acetylated compounds were obtained. An intense fragment ion at m/z 151 corresponding to (dimethylamino)ethylaminosulfonyl moiety was observed in each spectra, suggesting that these reagents were suitable for ESI-MS/MS analysis. DAABD-AE, DAABD-APy and DAABD-PZ were applied to the analysis of octanoic acid and it was found that DAABD-AE and DAABD-APy gave high signal intensity suitable for LC/ESI-MS/MS.

Rapid UPLC-MS/MS method for routine analysis of plasma pristanic, phytanic, and very long chain fatty acid markers of peroxisomal disorders

“…As an alternative approach, we aimed at preparing a hydrophobic derivative with high ionization efficiency. For this purpose, we utilized our recently developed reagent, DAABD-AE, known to form stable amides upon reaction with a carboxyl group (20)(21)(22). This reagent was developed with the convenient ESI in mind, and was thus designed to contain a readily chargeable moiety and a benzofurazan skeleton.…”

“…Recently, we described the synthesis of 4-[2-(N,N-dimethylamino)ethylaminosulfonyl]-7-(2-aminoethylamino)-2,1,3-benzoxadiazole (DAABD-AE) and demonstrated its potential as a derivatization reagent for carboxylic acids (20)(21)(22). Designed specifically for ESI-MS/MS, DAABD-AE contains an ionizable moiety with high proton affinity to improve the ionization process and a hydrophobic benzofurazan structure.…”

Historical review of sample preparation for chromatographic bioanalysis: pros and cons

“…Derivatization was usually used to enhance the sensitivity of nonionizable analytes [Higashi et al, 2007;Liu et al, 2006;Beaudry et al, 2006;L Xu and Spink, 2007;Santa et al, 2007] and for chiral separation [Berna and Ackermann, 2007;Szabó , 2001].…”

Highly sensitive and positively charged precolumn derivatization reagent for amines and amino acids in liquid chromatography/electrospray ionization tandem mass spectrometry

“…In the past, derivatization reagents have been developed for steroids (whose ionization efficiency in ESI‐MS is low), 2‐hydrazino‐1‐methylpyridine (HMP), 1‐(2,4‐dinitro‐5‐fluorophenyl)‐4‐methylpiperazine (PPZ), and 4‐(4‐methyl‐1‐piperazyl)‐3‐nitrobenzoyl azide (APZ) 10–13. Santa et al have developed benzofurazan derivatization reagents for carboxylic acids and aldehydes 14–19. Very recently, Shimbo et al have developed derivatization reagents for the high‐speed analysis of amino acids: p ‐ N , N , N ‐trimethylammonioanilyl N '‐hydroxysuccimidyl carbamate iodide (TAHS) and 3‐aminopyridyl‐ N ‐hydroxysuccimidyl carbamate (APDS) 20–22.…”

“…The following conditions should be satisfied when derivatization reagents are used in LC/MS/MS: (1) the derivatized analytes should have high ionization efficiency and they should be detected with high sensitivity; (2) it should react with the target functional group under mild conditions; (3) it should have a hydrophobicity that is appropriate for the separation of the derivatized analytes by a reversed‐phase system; (4) it should be less susceptible to ion suppression; (5) fragmentation of the target analytes could be accomplished more easily by collision‐induced dissociation (CID) and efficiently generate a particular product ion for sensitive MS/MS detection;16 and (6) it should be inexpensive and easily obtainable compared to the numerous conventional derivatization reagents that are commercially available. We have developed derivatization reagents for LC/MS/MS that meet these requirements.…”