LC-ESI-MS determination of quassinoids isobrucein B and neosergeolide in Picrolemma sprucei stem infusions

Abstract

Infusões dos caules de Picrolemma sprucei (pseudônimo: P. pseudocoffea) são principalmente utilizadas como antimaláricos em toda região amazônica. Desta espécie foram isolados os quassinoides isobruceína B e neosergeolida, os quais apresentam atividade antimalárica e citotóxica. Neste estudo, apresentamos o desenvolvimento de uma metodologia analítica por LC-(+)-ESI-MS/ MS visando a determinação dos principais quassinoides desta espécie. O método desenvolvido foi empregado para análise de uma formulação artesanal (infusão de 1 g de matéria seca -caules pulverizados de P. sprucei em 1 L de água fervente). Padrões previamente isolados de isobruceína B e neosergeolida foram utilizados para a determinação da linearidade na faixa de calibração entre 0,25 to 5 µg mL -1 e 0,5 a 10 µg mL -1 , respectivamente. Como padrão interno foi utilizada a substância fluoroglucinol na concentração de 4,0 µg mL -1 . Ambos os compostos apresentaram boa linearidade, precisão e exatidão e as concentrações de isobruceína B e neosergeolida obtidas nas infusões foram de 60,1 e 774 µg L -1 , respectivamente.Infusions of the stems of Picrolemma sprucei (pseudonym: P. pseudocoffea) are used in the Amazon regions of Peru, Brazil and French Guiana as antimalarials among other uses. They contain the bitter quassinoids isobrucein B (1) and neosergeolide (2) that have important antimalarial and toxic properties among others. In this study, an LC-(+)-ESI-MS/MS method was developed and applied to the determination of 1 and 2 in a common remedy prepared by infusing 1 g of dry, powdered stems of P. sprucei in 1 L of boiling water. Isolated 1 and 2 were used in calibration ranges of 0.25 to 5 µg mL -1 and 0.5 to 10 µg mL -1 , respectively, with the internal standard phloroglucinol at 4.0 µg mL -1 . Good linearity, precision and accuracy were observed for both compounds. The concentrations of 1 and 2 in the stem infusions were found to be 60.1 and 774 µg L -1 , respectively. Recently, P. sprucei has been the subject of several studies whose results in general lend support to its uses in traditional medicine. For example, leaf and stem infusions and other extracts have been shown to possess in vitro antihelminthic activity. 8 Also, an ethnopharmacological study in French Guiana showed that alcohol extracts of P. sprucei root, stem and bark are used in local traditional medicine as a curative treatment for malaria in association with Geissospermum spp. (Apocynaceae) and Quassia amara (Simaroubaceae) or modern drugs. 5 In a subsequent study, Bertani et al. 9 demonstrated that a P. sprucei water extract can inhibit hemozoin formation and in vitro assays demonstrated the antimalarial activity of this extract against the chloroquine-resistant Plasmodium falciparum strain W2. In the western Brazilian Amazon, dried stems are commonly commercialized in local marketplaces by traditional healers or raizeiros and are typically used in the preparation of infusions for oral ingestion. KeywordsInfusions of P. sprucei contain the quassinoids isobrucein B (1) and neos...

Development and Validation of Liquid Chromatography Combined with Tandem Mass Spectrometry Methods for the Quantitation of Simalikalactone E in Extracts of Quassia amara L. and in Mouse Blood

“…Pohlit et al . () described the quantitation of neosergeolide with a linearity range from 0.5 to 10 mg/L and LOQ of 0.5 mg/L, and isobrucein B with a linearity range of 0.25–5 mg/L and LOQ of 0.25 mg/L using HPLC–ESI(+)/triple quadrupole/MS/MS with MRM detection. Compared with the results herein, those described by Sarais et al .…”

“…More recently, Pohlit et al . () quantitated the quassinoids isobrucein B and neosergeolide in Picrolemma sprucei infusions using triple quadrupole HPLC with electrospray ionisation (ESI) MS/MS and multiple reaction monitoring (MRM), with limits of quantitation (LOQ) of 0.25 and 0.5 mg/L respectively. Sarais et al .…”

“…Vitányi et al (1997) described a reversed-phase high-performance (HP) LC-MS method with thermospray ionisation after post-column addition of ammonium acetate to quantitate the [M + H] + and [M + NH 4 ] + ions of three quassinoids (quassin, neoquassin and 18-hydroxyquassin). More recently, Pohlit et al (2009) quantitated the quassinoids isobrucein B and neosergeolide in Picrolemma sprucei infusions using triple quadrupole HPLC with electrospray ionisation (ESI) MS/MS and multiple reaction monitoring (MRM), with limits of quantitation (LOQ) of 0.25 and 0.5 mg/L respectively. Sarais et al (2010) detected quassin and neoquassin contained in the wood of Quassia amara, with a limit of detection (LOD) and LOQ of 0.5 and 1 μg/kg respectively for both compounds, by MRM transitions of their respective proton adduct precursor ions by HPLC-ESI/QTOF (quadrupole time-of-flight) MS/MS.…”

Cytotoxic Compounds from Brucea mollis

“…In particular, the cancerous cellular growth inhibitory activity of isobruceine B ( 2 ) was stronger than that of ellipticine, the positive control (IC 50 values ranging from 0.66–0.89 μg/mL). Isobruceine B was isolated from the wood of Brucea antidysenterica [15] with no biological activity reported, and from the stems of the Simaroubaceae Picrolemma sprucei plant, which was used in the Amazon regions of Peru, Brazil, and French Guiana as antimalarials [16]. Isobruceine B exhibited in vitro cytotoxic activities against SF-295, HCT-8, and HL-60 human tumor cells lines (IC 50 = 5–27 μg/L), and against the malarial multidrug-resistant Plasmodium falciparum K1 strain (IC 50 = 1.0–4.0 μg/L) [17].…”

Ethnobotany of Medicinal Plants Used to Treat Malaria by Traditional Healers from Ten Indigenous Colombian Communities Located in Vaupes Medio

“…In Brazil, French Guyana and Peru this plant is used for the treatment of malaria. 79 The family to which this species belongs, Simaroubaceae, contain quassinoids responsible for the anti-malaria, anti-cancer and antiamoebic activity. 38 The cuasinoide neosergeolide was isolated from the stem and root of this species, which has significant in vitro activity in multidrug resistant P. falciparum, being more active than quinone and chloroquine.…”