LC/MS/MS and radioisotope method combined for recognizing the affinity between catalpol and OCT2 transporter

Abstract

More and more herbal medicines are found to be the substrates of drug transporters. In this paper, chromatography/tandem mass spectrometry (LC/MS/MS) combined with radioisotope method was used for the quantification of catalpol, a traditional Chinese medicine, to study the affinity relationship between herbal medicines and transporters. Catalpol uptake experiment was carried out by using several transporters (OAT1, OCT2, OAT3, OATP1B1 and OATP2B1). And samples were precipitated with methanol and quantified with LC/MS/MS. The results show that catalpol has a good affinity with OCT2-transfected S2 cells. After studying drug-drug interaction between catalpol and ¹⁴C-tetraethylammonium (TEA), we found that catalpol is able to facilitate TEA transport mediated by OCT2, suggesting that catalpol could probably be a new promoter of OCT2.

Keywords

catalpol / LC/MS/MS / OCT2

References

[1] Giacomini K M, Huang S M, Tweedie D J, Benet L Z, Brouwer K L R, Chu X, Dahlin A, Evers R, Fischer V, Hillgren K M, Hoffmaster K A, Ishikawa T, Keppler D, Kim R B, Lee C A, Niemi M, Polli J W, Sugiyama Y, Swaan P W, Ware J A, Wright S H, Wah Yee S, Zamek-Gliszczynski M J, Zhang L. Membrane transporters in drug development. Nature Reviews. Drug Discovery, 2010, 9(3): 215–236

[2] Flynn C A, Alnouti Y, Reed G A. Quantification of the transporter substrate fexofenadine in cell lysates by liquid chromatography/tandem mass spectrometry. Rapid Communications in Mass Spectrometry, 2011, 25(16): 2361–2366

[3] Huang W J, Niu H S, Lin M H, Cheng J T, Hsu F L. Antihyperglycemic effect of catalpol in streptozotocin-induced diabetic rats. Journal of Natural Products, 2010, 73(6): 1170–1172

[4] Shieh J P, Cheng K C, Chung H H, Kerh Y F, Yeh C H, Cheng J T. Plasma glucose lowering mechanisms of catalpol, an active principle from roots of Rehmannia glutinosa, in streptozotocin-induced diabetic rats. Journal of Agricultural and Food Chemistry, 2011, 59(8): 3747–3753

[5] Wang Z, Liu Q, Zhang R, Liu S, Xia Z, Hu Y. Catalpol ameliorates beta amyloid-induced degeneration of cholinergic neurons by elevating brain-derived neurotrophic factors. Neuroscience, 2009, 163(4): 1363–1372

[6] Lu R, Gu Y, Si D, Liu C. Quantitation of catalpol in rat plasma by liquid chromatography/electrospray ionization tandem mass spectrometry and its pharmacokinetic study. Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences, 2009, 877(29): 3589–3594

[7] Li X E, Yang S L, Yang J S. Comparison and correlative analysis on characters of Rehmannia glutinosa Libosch. Varieties. Acta Academiae Medicinae Sinicae, 2001, 23(6): 560–562 (in Chinese)

[8] Tamura Y, Nishibe S. Changes in the concentrations of bioactive compounds in plantain leaves. Journal of Agricultural and Food Chemistry, 2002, 50(9): 2514–2518

[9] Wu H K, Chuang W C, Sheu S J. Separation of nine iridoids by capillary electrophoresis and high-performance liquid chromatography. Journal of Chromatography. A, 1998, 803(1): 179–187

[10] Suomi J, Sirén H, Wiedmer S K, Riekkola M L. Isolation of aucubin and catalpol from Melitaea cinxia larvae and quantification by micellar electrokinetic capillary chromatography. Analytica Chimica Acta, 2001, 429(1): 91–99

[11] Suomi J, Wiedmer S K, Jussila M, Riekkola M L. Determination of iridoid glycosides by micellar electrokinetic capillary chromatography-mass spectrometry with use of the partial filling technique. Electrophoresis, 2001, 22(12): 2580–2587

[12] Suomi J, Wiedmer S K, Jussila M, Riekkola M L. Analysis of eleven iridoid glycosides by micellar electrokinetic capillary chromatography (MECC) and screening of plant samples by partial filling (MECC)-electrospray ionisation mass spectrometry. Journal of Chromatography. A, 2002, 970(1): 287–296

[13] Suomi J, Sirén H, Jussila M, Wiedmer S K, Riekkola M L. Determination of iridoid glycosides in larvae and adults of butterfly Melitaea cinxia by partial filling micellar electrokinetic capillary chromatography-electrospray ionisation mass spectrometry. Analytical and Bioanalytical Chemistry, 2003, 376(6): 884–889

[14] Helfrich E, Rimpler H. Iridoid glycosides from Gmelina philippensis. Phytochemistry, 2000, 54(2): 191–199

[15] Bowers M D. Hostplant suitability and defensive chemistry of the Catalpa sphinx, Ceratomia catalpae. Journal of Chemical Ecology, 2003, 29(10): 2359–2367

[16] Fan L, Zhang W, Guo D, Tan Z R, Xu P, Li Q, Liu Y Z, Zhang L, He T Y, Hu D L, Wang D, Zhou H H. The effect of herbal medicine baicalin on pharmacokinetics of rosuvastatin, substrate of organic anion-transporting polypeptide 1B1. Clinical Pharmacology and Therapeutics, 2008, 83(3): 471–476

[17] Liu C X, Yi X L, Si D Y, Xiao X F, He X, Li Y Z. Herb-drug interactions involving drug metabolizing enzymes and transporters. Current Drug Metabolism, 2011, 12(9): 835–849

RIGHTS & PERMISSIONS

Higher Education Press and Springer-Verlag Berlin Heidelberg