Determination of the Plasma Pharmacokinetic and Tissue Distributions of Swertiamarin in Rats by Liquid Chromatography with Tandem Mass Spectrometry

Abstract

An LC-MS/MS method was developed for the quantification of swertiamarin (CAS 17388-39-5) in rat plasma and tissues using gentiopicroside as the internal standard (IS). Swertiamarin and an IS were extracted from plasma and tissues by a simple solid-phase extraction (SPE) procedure. Separation was achieved on a Phenomenex kinetex-C₁₈ column (100 mm×2.1 mm, 2.6 µm) with an isocratic mobile phase consisting of methanol and water (22:78, v/v) with 0.1% acetic acid at a flow rate of 0.2 mL/min. The analyte and IS were detected by negative ion electrospray ionisation in multiple-reaction monitoring mode while monitoring the transitions of m/z 433 [M + CH₃COO]⁻→179 and m/z 415 [M + CH₃COO]⁻→179 for swertiamarin and the IS, respectively. The method was validated with respect to selectivity, matrix effect, linearity, accuracy, precision, recovery and stability. The method was successfully applied in a pharmacokinetic study of swertiamarin after intravenous and oral administration to rats. The pharmacokinetics of swertiamarin showed rapid absorption and elimination, and its absolute bioavailability was low at 10.3%. After oral administration to rats, swertiamarin was rapidly and widely distributed in its tissues. High concentrations were found in the liver and kidney, indicating that swertiamarin was possibly absorbed in the liver and eliminated by the kidney.

Key words

CAS 17388-39-5 - LC-MS/MS - rat - plasma - tissues

• References

• 1 Ayyanar M, Ignacimuthu S. Traditional knowledge of Kani tribals in Kouthalai of Tirunelveli hills, Tamil Nadu, India. J Ethnopharmacol 2005; 102: 246-255
• 2 Ma LN, Tian CW, Zhang TJ et al. Advances in study on iridoids in plants of Swertia L·and their pharmacological activity. Chin Tradit Herb Drugs 2008; 39: 790-795
• 3 Alam KD, Ali MS, Mahjabeen S et al. Report: analgesic activities of ethanol extract of leaf, stem and their different fractions of Swertia chirata. Pak J Pharm Sci 2010; 23: 455-457
• 4 Ramesh N, Viswanathan MB, Saraswathy A et al. Antimicrobial and phytochemical studies of Swertia corymbosa. Fitoterapia 2002; 73: 160-164
• 5 Kumarasamy Y, Nahar L, Cox PJ et al. Bioactivity of secoiridoid glycosides from Centaurium erythraea. Phytomedicine 2003; 10: 344-347
• 6 Kimura Y, Sumiyoshi M. Effects of Swertia japonica extract and its main compound swertiamarin on gastric emptying and gastrointestinal motility in mice. Fitoterapia 2011; 82: 827-833
• 7 Vaidya H, Rajani M, Sudarsanam V et al. Swertiamarin: A lead from Enicostemma littorale Blume. for anti-hyperlipidaemic effect. Eur J Pharmacol 2009; 617: 108-112
• 8 Jaishree V, Badami S, Rupesh Kumar M et al. Antinociceptive activity of swertiamarin isolated from Enicostemma axillare. Phytomedicine 2009; 16: 227-232
• 9 Vaijanathappa J, Badami S. Antiedematogenic and Free Radical Scavenging Activity of Swertiamarin Isolated from Enicostemma axillare. Planta Med 2009; 75: 12-17
• 10 Jaishree V, Badami S. Antioxidant and hepatoprotective effect of swertiamarin from Enicostemma axillare against D-galactosamine induced acute liver damage in rats. J Ethnopharmacol 2010; 130: 103-106
• 11 Suryawanshi S, Asthan RK, Gupta RC. Simultaneous estimation of mangiferin and four secoiridoid glycosides in rat plasma using liquid chromatography tandem mass spectrometry and its application to pharmacokinetic study of herbal preparation. J Chromatogr B 2007; 858: 211-219
• 12 Li HL, Peng XJ, He JC et al. Development and validation of a LC-ESI–MS/MS method for the determination of swertiamarin in rat plasma and its application in pharmacokinetics. J Chromatogr B 2011; 879: 1653-1658