Isothiocyanates as derivatization reagents for amines in liquid chromatography/electrospray ionization–tandem mass spectrometry

Abstract

The applicability of 3-pyridyl isothiocyanate, p-(dimethylamino)phenyl isothiocyanate and m-nitrophenyl isothiocyanate as the derivatization reagents for amines in high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) was examined. The generated derivatives of amines with these reagents were favorably separated on the reversed-phase column and detected by ESI-MS/MS. The C-N bond of the generated thiourea structure was efficiently cleaved by collision-induced dissociation and gave the single and intense product ion. Among the three reagents, 3-pyridyl isothiocyanate was the most suitable as the derivatization reagent with regard to the reactivity to amines and the detection sensitivity.

Derivatization reagents in liquid chromatography/electrospray ionization tandem mass spectrometry

“…Their generated derivatives gave the intense product ions at m/z 137, m/z 179 and m/z 137, respectively (Fig. 4b; Santa, 2010).…”

Compounds having thiourea moiety as derivatization reagents in liquid chromatography/electrospray ionization–tandem mass spectrometry (LC/ESI‐MS/MS): synthesis of derivatization reagents for carboxylic acids

“…In the previous paper, we have reported that the compounds having an isothiocyanate group were suitable as the derivatization reagents for amines in LC/ESI‐MS/MS. The generated compounds, having thiourea structure, efficiently produced a particular fragment ion by CID (Santa, 2010). It was also reported that the compounds having thiourea structure often gave the clear product ion spectra (Claeson et al ., 2004; Ji and Morris, 2003).…”

“…These include p ‐ N , N , N ‐trimethylaminoaninyl‐ N '‐hydroxysuccinimidyl carbomate iodide (TAHS) (Shimbo et al ., 2009a), 3‐aminopyridyl‐N‐hydroxysuccinimidyl carbamate (APDS) (Shimbo et al ., 2009b) for amines, 2‐hydrazino‐1‐methylpyridine (HMP) (Higashi et al ., 2005a), 4‐[2‐( N , N ‐dimethylamino)ethylaminosulfonyl]‐7‐ N ‐methylhydrazino‐2,1,3‐benzoxadiazole (DAABD‐MHz) (Santa et al ., 2008) for ketones, isonicotinoyl azide (NA) (Higashi et al ., 2007) for alcohols, dansyl chloride for phenols and 4‐[2‐( N , N ‐dimethylamino)ethylaminosulfonyl]‐7‐(2‐aminoethylamino)‐2,1,3‐benzoxadiazole (DAABD‐AE) for carboxylic acids (Al‐Dirbashi et al ., 2008; Santa et al, 2007b; Tsukamoto et al ., 2005). In the previous paper, we reported that the compounds with a thiourea structure, generated by the reaction of amines with isothiocyanates, afforded a particular product ion efficiently by CID and were suitable for the MS/MS detection (Santa, 2010).…”

Design and synthesis of a novel pre-column derivatization reagent with a 6-methoxy-4-quinolone moiety for fluorescence and tandem mass spectrometric detection and its application to chiral amino acid analysis

“…The values of LLOD using these methods were 50-500 amol/injection. Several HPLC-MS/MS reagents with pyridinyl moieties, 3-pyridyl isothiocyanate (Py-NCS) and 3-aminopyridyl-N-hydroxysuccimidyl carbamate (APDS), have also been reported [18,35]. These reagents are also used for highly sensitive determination of amino compounds by HPLC-MS/MS.…”