Simultaneous Determination and Pharmacokinetics Study of Six Triterpenes in Rat Plasma by UHPLC-MS/MS after Oral Administration of Sanguisorba officinalis L. Extract

Abstract

A selective and sensitive ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the determination of ziyuglycoside I (I), 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester (II), 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester (III), rosamultin (IV), 1β-hydroxyeuscaphic acid (V) and alpinoside (VI) in rats after oral administration of Sanguisorba officinalis L. (S. officinalis) extract. The 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside in rat plasma were the first report in the pharmacokinetics study in the present study. The analytes were quantified using the multiple reaction monitoring (MRM) mode with the electrospray ion source in positive electrospray ionization. Plasma was extracted with ethyl acetate via liquid–liquid extraction. Bifendate was used as internal standard (IS). The current method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery, matrix effect and stability. The lower limits of quantification of ziyuglycoside I, 3β,19α-dihydroxyurs-12-en-28-oic-acid 28-β-d-glucopyranosyl ester, 3β-[(α-l-arabinopyranosyl) oxy]-urs-12,18(19)-dien-28-oic acid β-d-glucopyranosyl ester, rosamultin, 1β-hydroxyeuscaphic acid and alpinoside were 6.1, 4.9, 1.3, 3.8, 1.5 and 5.7 ng/mL, respectively. Intra-day and inter-day precision and the accuracy of the assay were in range from −9.48 to 12.74%. The extraction recoveries of analytes and bifendate (IS) from rat plasma ranged from 77.17% to 92.48%. Six compounds could be rapidly absorbed into blood (Tmax, 0.58–1.58 h), and then eliminated relatively slowly (t1/2, 6.86–11.63 h). The pharmacokinetic results might contribute to further guide the clinical application of S. officinalis.

Comparison of the pharmacokinetic profiles of 13 phenolic acids and 6 triterpenes in normal and leukopenia rats after oral administration of Sanguisorba officinalis L. extract by LC‐MS/MS

“…The phenolic acids had good signal responses in the negative ion mode but no responses in positive ion mode. The triterpenes could only be analyzed by positive ESI mass spectrometry according to a previous study [19]. Thus, ESI operated in negative mode was selected as the ionization source for the 13 phenolic acids ( I–XIII ), and the positive mode was selected as the ionization source for the six triterpenes ( XIV–XIX ).…”

“…In this study, a selective, accurate, and efficient UHPLC-ESI MS/MS method was developed for the simultaneous determination of 13 phenolic acids. Moreover, for more comprehensively determining the chemical constituents in the S. officinalis extract, the method for simultaneous determination of 6 triterpenes in previous study was also employed [19]. Thus, two methods were used to ensure the comprehensiveness and reliability of this study.…”

“…It has been officially recorded in the Chinese Pharmacopoeia (2015); possesses activities such as detoxification, analgesia, and hemostasis; and has been used for the prevention and treatment of various diseases in tradition, including burns and scalds, bleeding hemorrhoids, and metrostaxis, bleeding wounds, hematochezia, and swollen carbuncles [15–18]. Sanguiin H‐4 ( I ), bergenin monohydrate ( II ), 3,3′‐dimethoxyellagic acid ( III ), ellagic acid ( IV ), (+)‐catechin monohydrate ( V ), methyl 3,4‐dihydroxy‐5‐methoxybenzoate ( VI ), ethyl 3,4,5‐trihydroxybenzoate ( VII ), syringic acid ( VIII ), ferulic acid ( IX ), caffeic acid ( X ), gallic acid ( XI ), p ‐coumaric acid ( XII ), 4‐hydroxybenzoic acid ( XIII ), ziyuglycoside I ( XIV ), 3 β ‐[( α ‐L‐arabinopyranosyl) oxy]‐urs‐12,18(19)‐dien‐28‐oic acid β ‐ d ‐glucopyranosyl ester ( XV ), rosamultin ( XVI ), alpinoside ( XVII ), 3 β ,19 α ‐dihydroxyurs‐12‐en‐28‐oic‐acid 28‐ β ‐ d ‐glucopyranosyl ester ( XVIII ), and hydroxyeuscaphic acid ( XIX ) are all the active components isolated from S. officinalis , and has been reported to possess an extensive range of pharmacological activities [19,20]. Accordingly, it has been noted that sanguiin H‐4 decreases procaspase‐3 associated with human poly(ADP‐ribose) polymerase cleavage and increases the activity of caspase‐3 in HL‐60 cells, without affecting normal human peripheral blood mononuclear cells, suggesting that sanguiin H‐4 may be a new candidate for drug development in the prevention and treatment of cancer [21].…”

“…Several studies have reported that various analytical methods, including colorimetry, high‐performance TLC, HPLC‐UV, LC–MS/MS, and UHPLC‐MS/MS, have been used in the qualitative or quantitative analysis of the phenolic acids and triterpenes [19,20,27]. Nonetheless, these methods have primarily focused on high concentrations of ingredients in S. officinalis or other plants.…”

The design and development of covalent protein-protein interaction inhibitors for cancer treatment

“…Different strategies are needed to design covalent PPI inhibitors compared to non-covalent inhibitors [48][49][50]. Covalent inhibitors traditionally target cysteine; however, their natural abundance is low and these residues have unique reactivity in proteome.…”