Journal of Pharmaceutical and Biomedical Analysis
Short communicationA rapid LC/MS/MS quantitation assay for naringin and its two metabolites in rats plasma
Introduction
Naringin (4′,5′,7-trihydroxy flavanone-7-rhamnonglucoside) is a flavonoid present in many Citrus fruits and traditional Chinese medicines [1], [2]. Like most flavonoids, naringin has anti-inflammatory [3], anti-ulcer [4], superoxide, and antioxidation [5] activities. Early research has shown that orally administered naringin can be metabolized into naringenin and naringenin glucuronide [6], [7], [8]. Naringenin, the aglycone of naringin, has also been found to exhibit anti-ulcer [4], antioxidant [5], and inhibition of breast cancer proliferation [9]. Several liquid chromatographic methods with UV-detection for detecting naringin in rabbit plasma [6], human plasma [7], human urine [8], and grapefruit juice have been developed. Ishii et al., reported the limits of detection by an assay in human urine was approximately 5 ng for naringin and 1 ng for naringenin [8], which is not sensitive enough to assay the plasma concentration of naringin due to the low oral dosage. To this day, research using the HPLC method with UV-detection to assay the naringin metabolite are unable to assay the naringin and its metabolite naringenin concurrently. Lack of specificity and low sensitivity still limit the effective detection of naringin and its metabolites.
The LC/MS/MS is a method that provides superior selectivity, sensitivity and a rapid rate of analysis. The method is accurate and highly sensitive for detecting plasma concentration in pharmacokinetics which accounts for its increasing popularity [10], [11], [12], [13], [14], [15], [16]. Our research established this new method of using LC/MS/MS for the determination of naringin and its metabolite naringenin concurrently in the plasma of Sprague-Dawley male rats.
Section snippets
Materials and reagents
Naringin and naringenin were purchased from Sigma (St. Louis, MO, purity >95%), while the internal standard (IS) hesperidin, was purchased from the National Institute for the control of pharmaceutical and biological products (HPLC grade). Stock solutions of naringin, naringenin and hesperidin were prepared by dissolving them in methanol. All other chemicals and solvents were of analytical-reagent grade and were used without further purification.
Instrumentation
Analyses were performed using a SHIMADZU HPLC
LC/MS/MS assay
Under ESI conditions, naringin gave MH+ at m/z 581.3 as the base ion, naringenin and hesperidin gave MH+ at m/z 273.4 and m/z 611.5 as the base ion. The ions m/z 581.3, 273.4 and 611.5 were selected for collision-induced dissociation (CID) experiments. Naringin generated one major product ion at m/z 273.4 (Fig. 1A), naringenin generated two product ions at m/z 147.1 and m/z 153.1 (Fig. 1B), and hesperidin generated two product ions at m/z 449.1 and 303.4 (Fig. 1C).
The precursor/product ion
Discussion
Naringin considered the most potent okadaic acid-antagonistic flavonoid, has been shown to exhibit bioactivity in a number of different ways such as anti-inflammatory [3], anti-ulcer [4], superoxide, and antioxidation [5]. Previous methods were used HPLC-UV to detect the naringin and its metabolites. Compared with the HPLC method, the lower limits of this method for naringin was 0.5 ng/ml, approximately 100 times higher than that of HPLC. Compared with LC/MS/MS, the HPLC method cannot detect
Conclusion
A highly sensitive and specific LC/MS/MS method for the quantification of naringin and its two metabolites was developed and successfully applied to investigate the pharmacokinetics of naringin following oral administration in Sprague-Dawley male rats.
Acknowledgements
Authors are grateful to the SINOVA Medicine Technology Development Limited Company for technical and mass spectrometer facility support.
References (16)
- et al.
J. Chromatogr.
(1993) - et al.
Life Sci.
(2002) - et al.
J. Chromatogr. B
(1996) - et al.
J. Chromatogr. B
(1997) - et al.
J. Pharm. Biomed. Anal.
(2003) - et al.
J. Pharm. Biomed. Anal.
(2000) - et al.
J. Pharm. Biomed. Anal.
(2004) - et al.
J. Chromatogr. B
(2003)
Cited by (105)
Recent advances and prospects in naringin nanocarrier drug delivery system for cancer management
2024, Journal of Drug Delivery Science and TechnologyNaringin: A potential natural product in the field of biomedical applications
2021, Carbohydrate Polymer Technologies and ApplicationsAssessing the effect and related mechanism of naringenin on the proliferation, osteogenic differentiation and endothelial differentiation of human periodontal ligament stem cells
2021, Biochemical and Biophysical Research CommunicationsRegulation effects of naringin on diesel particulate matter-induced abnormal airway surface liquid secretion
2019, PhytomedicineCitation Excerpt :Naringenin (Fig. 1B), the aglycone of naringin, can also be found but to a lesser extent in regular diet. Researches of naringin pharmacokinetics have suggested that naringenin is the main existent form in serum after oral administration of naringin because naringin can be metabolized into naringenin by liver and intestine (Fang et al., 2006; Hsiu et al., 2002; Zeng et al., 2017). Previous studies have indicated that naringenin exhibited expectorant effects by increasing ASL secretion through regulating activation and expression of CFTR in airway epithelial cells (Shi et al., 2017).