A Pharmacokinetic Study by LC-MS/MS to Quantify Isoquercetin and Astragalin in Rat Serum After Oral Administration of a

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ORIGINAL ARTICLE

A Pharmacokinetic Study by LC-MS/MS to Quantify Isoquercetin and Astragalin in Rat Serum After Oral Administration of a Combined Extract of Moringa oleifera and Centella asiatica Mohd Salleh Rofiee 1,2

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Mohd Izwan Mohamad Yusof 1

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Teh Lay Kek 1,3

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Mohd Zaki Salleh 1

Received: 7 July 2020 / Accepted: 18 September 2020 # Sociedade Brasileira de Farmacognosia 2020

Abstract TGT-PRIMAAGE is a combination of leaf extracts from Moringa oleifera Lam, Moringaceae, and Centella asiatica (L.) Urb., Apiaceae. It was previously proven on its potentials to reduce oxidative stress and senescence in hydrogen peroxide–induced human dermal fibroblasts and to improve in memory and learning abilities. This mixture is rich in phenolic and flavonoids, which include astragalin and isoquercetin. The aim of this study was to develop and validate an analytical method by liquid chromatography coupled to tandem mass spectrometry to determine the pharmacokinetic parameters of astragalin and isoquercetin in a rat model. A single dose of extract (5000 mg/kg) was administrated orally to 5 male Sprague Dawley rats. Sera were prepared from 500 μl of blood samples collected from orbital sinus at baseline and 10 different time points. Samples were extracted by liquid-liquid extraction before analyses using ultra-high-performance liquid chromatography coupled with a triple quadrupole. After oral administration of the extract, astragalin and isoquercetin achieved maximum serum concentration of 3.80 ± 0.38 ng ml−1 at 6 ± 2.24 min and 18.33 ± 7.88 ng ml−1 at 7.00 ± 2.73 min, respectively. The half-life (T1/2) for astragalin was 125.95 ± 68.58 min and for isoquercetin was 153.54 ± 81.44 min. Current findings demonstrated that these compounds were rapidly adsorbed after oral administration with a short half-life of 2 to 3 h. Keywords Flavonoid quantification . Pharmacokinetics . Serum . Quantification method

Introduction TGT-PRIMAAGE is a combination of leaf extracts from Moringa oleifera Lam, Moringaceae, and Centella asiatica (L.) Urb., Apiaceae. Moringa oleifera is referred as the ‘drumstick tree’, ‘miracle tree’, ‘horse radish tree’, or the ‘kelor tree’ (Anwar and Bhanger 2003; Gopalakrishnan et al. 2016). This Electronic supplementary material The online version of this article (https://doi.org/10.1007/s43450-020-00105-6) contains supplementary material, which is available to authorized users. * Teh Lay Kek [email protected] 1

Integrative Pharmacogenomics Institute, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia

2

Faculty of Health Science, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia

3

Department of Pharmaceutical Life Sciences, Faculty of Pharmacy, Universiti Teknologi MARA Selangor, Puncak Alam, Malaysia

plant is widely cultivated in Asian and African countries (Nayak et al. 2016). The leaves have been used traditionally for treatment of constipation, headache, arthritis, diabetes, hypertension, and typhoid fever (Anwar et al. 2007). Chemical analysis of these plants indicates that it

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