General Fragmentations of Alkaloids in Electrospray Ionization Tandem Mass Spectrometry

Abstract

Various types of alkaloids observed in several herbal medicines were analyzed by electrospray ionization tandem mass spectrometry in positive ion mode. In the present study, MS/MS spectralpatterns were investigated for eight-types of alkaloids (aporpine, protoberberine, tetrahydroprotoberberine, benzylisoquinoline, protopine, phthalide, morpine, and bisbenzylisoquinoline). For aporpine-and protoberberine-type alkaloids, main fragmentations occurred at substituted groups on rigid ring structures, not showing ring fusion. Interesting fragmentations due to iminolization and retro-Diels-Alder (RDA) reaction were observed in MS/MS spectra of protopine-and tetrahydroprotobereberine-type alkaloids. Also, several types of fragmentations such as inductive cleavage and α-cleavage, or bond cleavage between two ring structures were observed depending on their structural characteristics. These fragmentation patterns are expected to allow instant classification of the specific alkaloid type in various MS/MS spectra of alkaloids.

Direct infusion ESI‐IT‐MSn alkaloid profile and isolation of tetrahydroharman and other alkaloids from Bocageopsis pleiosperma maas (Annonaceae)

“…Note: A, Aporphine; B, benzylisoquinoline; T, tetrahydroprotoberberine; O, others; d, Stévigny et al ., ; e, Schmidt et al ., ; f, Shim et al ., .…”

“…An ion at m / z 178 was previously observed in the electron ionisation (EI) MS of tetrahydroprotoberberine alkaloids containing methoxyl and a hydroxyl groups at the ring A, such as scoulerine and caseamine (Chen and Maclean, ). In ESI‐MS experiments it was suggested that this diagnostic ion is formed via a RDA ring opening of the protonated molecule (Shim et al ., ) (Fig. ).…”

“…In contrast to the m /z 328 detected in the twig extract, the ion at m / z 328 in the bark extract fragmented to give a major ion at m / z 178 and a minor ion at m / z 151 consistent with a single (Fig. 9S) tetrahydroprotoberberine compound (Shim et al ., ) (Fig. ).…”

“…Investigations using tandem mass spectrometry (MS n ) demonstrated that benzylisoquinoline alkaloids possess a set of key fragmentation patterns, from which it is possible to determine the substituents in the benzyl and the isoquinoline moieties (Schmidt et al, 2005); aporphines have fragmentation patterns that are useful for the characterisation of different substituent groups on the main aporphine skeleton (mainly in rings A and D) (Stévigny et al, 2004); and tetrahydroprotoberberine alkaloids fragment through a retro-Diels-Alder (RDA) pattern, which enables the determination of the A and D rings substitutions (Shim et al, 2013). Thus, the tentatively characterisation of these compounds in complex mixtures enables the prioritisation of unknown compounds to be selected for further isolation steps.…”

Capillary‐HPLC with tandem mass spectrometry in analysis of alkaloid dyestuffs – a new approach

“…Tetrahydroprotoberberines undergo fragmentation via cleavage of the C aromatic ring. For benzyltetrahydroisoquinoline or aporphine alkaloids, elimination of dimethylamine from ammonium group, followed by loss of small molecules, such as methane, methanol or carbon monoxide is observed .…”