Hydrazide and Hydrazine Reagents as Reactive Matrices for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry to Detect Steroids with Carbonyl Groups

Abstract

Fifty-one reagents (37 hydrazides and 14 hydrazines) were examined to determine if they could function as reactive matrices for the detection of steroids with carbonyl groups in matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS). Among these reagents, 3-hydroxy-2-naphthoic acid hydrazide reacted most efficiently with steroids with carbonyl groups, allowing detection of them at the 1pmol level. Results from accurate mass measurement with a JMS-S3000 Spiral-TOF suggested that the ion peaks corresponding to the protonated fragment of a hydrazone were observed, in addition to the protonated molecular peaks of the resulting hydrazones ([M(D)+H](+)) and their sodium adduct ([M(D)+Na](+)). 3-Hydroxy-2-naphthoic acid hydrazide also could detect cortisol (1.93ng) spiked in a human serum certified reference material, as well as cortisone and cortisol in a human saliva sample collected in the morning. Using a combination of 3-hydroxy-2-naphthoic acid hydrazide and α- cyano-4-hydroxycinammic acid (CHCA) (3-hydroxy-2-naphthoic acid hydrazide:CHCA=4:1, v/v), even cortisone and cortisol in a human saliva sample collected in the afternoon, when levels are typically low, could be detected effectively.

Veni, Vidi, Vici: Immobilized Peptide-Based Conjugates as Tools for Capture, Analysis, and Transformation

“…The carbonyl moiety can be found in a wide variety of organic compounds. In living organisms, it is present in the form of ketone bodies-compounds primarily derived from fatty acids [21], steroids, including important steroid hormones [22], and α,β-unsaturated aldehydes and γ-ketoaldehydes, with strong neurotoxic properties [23]. A few new psychoactive substances, especially cathinone derivatives, also contain carbonyl.…”

Strategies to diversify natural products for drug discovery

“…The carbonyl group, one of the major chemical functionalities, is commonly found in the structures of natural products. This kind of functional group, which includes ketones, ester, aldehydes, and amides, can react with hydrazine to form either hydrazones or acyl hydrazides . Carbonyl group transformation by hydrazine could lead to the diversification of components of natural extracts, which not only increases the nitrogen content in natural product‐like compounds but also increases the nucleophilic character, inducing further reactions .…”

2-Hydrazinoquinoline: A Reactive Matrix for Matrix-Assisted Laser Desorption/Ionization Mass Spectrometry to Detect Gaseous Carbonyl Compounds

“…In consequence, we found that some hydrazide and hydrazine reagents reacted with the carbonyl groups of measured samples, such as steroids, and that their resulting derivatives (hydrazones) could be effectively detected in MALDI-MS without the addition of conventional MALDI-MS matrices. 5 These hydrazide and hydrazine reagents functioned as reactive matrices for MALDI-MS. We further reported that two hydrazide (2-hydroxybenzohydrazide and 3-hydroxy-2-naphthoic acid hydrazide) and two hydrazine [2-hydrazinoquinoline and 2,4-dinitrophenylhydrazine (DNPH)] reagents could react efficiently with carbonyl groups of gaseous aldehydes (formaldehyde, acetaldehyde, and propionaldehyde), the main agents for sick-building syndrome, 6 operate as reactive matrices for them, and detect them at a single step in MALDI-MS. 7 Up until now, several groups have reported different potential reactive matrices for MALDI-MS. These include: (i) DNPH, a well-known derivatization reagent for carbonyl groups, which was utilized as a reactive matrix to measure corticosteroids in MALDI-MS coupling to capillary high-performance liquid chromatography (HPLC); 8 (ii) 4-dimethylamino-6-(4-methoxy-1-naphthyl)-1,3,5-triazine-2-hydrazine (DMNTH), was exploited as a derivatization reagent for a carbonyl group and used to detect a wide range of carbonyl compounds in laser desorption/ionization (LDI) MS; 9 (iii) 9-(3,4-diaminophenyl) acridine was utilized for measuring a-dicarbonyls with a limit of detection of <0.3 ng mL -1 in LDI-MS; 10 (iv) [(E)-4-(2-cyano-2-carboxyvinyl)phenyl]boronic acid selectively detected vicdiols, a-hydroxyacids, aminol, and Fanions in water as a reactive matrix for MALDI-MS; 11 (v) DMNTH was superior to DNPH as a reactive matrix for the detection of glucocorticoids in MALDI-MS imaging; 12 (vi) pyrylium salts, such as 2,4-diphenyl-pyranylium salts, that reacted efficiently with various bioactive primary amines (e.g., dopamine and amphetamine) were useful in MALDI-MS imaging; 13 and (vii) 2,5-dihydroxyacetophenone, an aromatic carbonyl compound, was a potential reactive matrix for the analyses of mono-, di-, and polyamines.…”