An Electron-Capture Dienophile Derivatization Agent for Increasing Sensitivity: Determination of a Vitamin D Analog (Ro 24-2090) in Plasma Samples with Liquid Chromatography/Mass Spectrometry

Application of Cookson‐type reagents for biomedical HPLC and LC/MS analyses: a brief overview

“…The best detectability in ESI-MS has been achieved for the analysis of compounds that are either ionic or can be readily ionized in solution. The derivatization with the Cookson-type reagents can enhance the proton-affinity of the analyte owing to the TAD moiety as already described, leading Figure 1j)] (Higashi, Yamauchi, & Shimada, 2003) or pentafluorobenzyl group [4-pentafluorobenzyl-TAD ( Figure 1k)] (Wang, Davis, Crews, Gabriel, & Edom, 1996) at the 4-position of TAD is favorable for the electron capture APCI-MS and particle-beam negative ionization MS, respectively. It is also desirable for the analyte to have a suitable fragmentable structure for selected reaction monitoring (SRM) detection.…”

“…A Cookson‐type reagent having the easily oxidizable ferrocene residue [4‐ferrocenylmethyl‐TAD (Figure i)] has also been developed for the LC/(+) ESI‐MS/MS of a VD analog (Murao, Ishigai, Sekiguchi, Takahashi, & Aso, ). On the other hand, the introduction of an electron‐affinitive moiety, such as a nitro group [4‐(4‐nitrophenyl)‐TAD (Figure j)] (Higashi, Yamauchi, & Shimada, ) or pentafluorobenzyl group [4‐pentafluorobenzyl‐TAD (Figure k)] (Wang, Davis, Crews, Gabriel, & Edom, ) at the 4‐position of TAD is favorable for the electron capture APCI‐MS and particle‐beam negative ionization MS, respectively. It is also desirable for the analyte to have a suitable fragmentable structure for selected reaction monitoring (SRM) detection.…”

Quantitative liquid chromatographic and tandem mass spectrometric determination of vitamin D3 in human serum with derivatization: A comparison of in-tube LLE, 96-well plate LLE and in-tip SPME

“…At the same time, these derivatives may also distinguish themselves from other interferences due to a significant increase in the molecular mass and their detection in the higher mass range together with a different fragmentation in the ion source. A variety of analogs and metabolites of vitamin D compounds have been derivatized with different triazolinediones [14][15][16][17][18]21,22] for structural confirmation, among them P-TAD. However, the P-TAD was never used as a derivatizing reagent for quantitative determination of I in plasma or serum samples.…”

Determination of 24,25‐dihydroxyvitamin D3 in human plasma using liquid chromatography‐mass spectrometry after derivatization with a Cookson‐type reagent

“…One of the reasons for this is the low ionization efficiency of natural vitamin D metabolites in various ionization methods. To overcome this problem, derivatives with Cookson-type reagents (4-substituted 1,2,4-triazoline-3,5-dione) have been examined in various ionization methods (Vreeken et al, 1993;Wilson et al, 1993;Yeung et al, 1995;Wang et al, 1996;Higashi et al, 1999a). These reagents consist of a powerful dienophile (triazolinedione) which reacts with the s-cis diene of the vitamin D compound and a substituent which increases the ionization efficiency of the resulting adduct in various ionization methods.…”

“…Yeung et al have examined the metabolism of a synthetic analog, 1,25-dihydroxy-16-yne vitamin D 3 , using LC-electrospray ionization (ESI)-MS after derivatization with 4-phenyl-1,2,4-triazoline-3,5-dione (PTAD) (Yeung et al, 1995). The LC-particle-beam electroncapture negative ionization-MS method employing derivatization with 4-pentafluorobenzyl-1,2,4-triazoline-3,5-dione for determination of an analog, Ro 24-2090, in plasma has also been reported (Wang et al, 1996). However, these methods are unsuitable for routine analysis because, to meet the demand of each interface, they employed capillary LC and normal-phase LC, respectively, which perform poorly in analysis of a complex matrix containing polar components.…”