Two-step liquid-phase microextraction and high-performance liquid chromatography for the simultaneous analysis of the enantiomers of mefloquine and its main metabolite carboxymefloquine in plasma
Abstract
A method for the simultaneous analysis of the enantiomers of mefloquine (MQ) and its main metabolite carboxymefloquine (CMQ) in plasma is described for the first time. The assay involves two-step liquid-phase microextraction (LPME) and enantioselective high-performance liquid chromatography. In the first LPME step, the enantiomers of MQ were extracted from an alkalinized sample through a thin layer of di-n-hexyl ether immobilized in the pores of the hollow fiber and into 0.01 M perchloric acid as acceptor solution. In the second LPME step, the same sample was acidified to enable the extraction of CMQ using the same organic solvent and 0.05 M sodium hydroxide as acceptor phase. The analytes were resolved on a Chirobiotic T column in the polar-organic mode of elution and detected at 285 nm. The recovery rates from 1 mL of plasma were in the range 35–38%. The method presented limits of quantification of 50 ng/mL for all analytes and was linear up to 1,500 and 3,000 ng/mL for the enantiomers of MQ and CMQ, respectively. The plasmatic concentrations of (+)-(RS)-MQ were higher than those of (−)-(SR)-MQ after oral administration of the racemic drug to rats.
Extraction device for LPME employing hollow fiber membranes used in the developed method
Keywords
Mefloquine enantiomers Carboxymefloquine Liquid-phase microextraction Liquid chromatography Plasma samplesNotes
Acknowledgments
The authors are grateful to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) for granting financial support and research fellowships.
References
- 1.Palmer KJ, Holliday SM, Brogden RN (1993) Drugs 45:430–475CrossRefGoogle Scholar
- 2.Brocks DR, Mehvar R (2003) Clin Pharmacokinet 42:1359–1382CrossRefGoogle Scholar
- 3.Basco LK, Gillotin C, Gimenez F, Farinotti R, Le Bras J (1992) Br J Clin Pharmacol 33:517–520Google Scholar
- 4.Karle JM, Olmeda R, Gerena L, Milhous WK (1993) Exp Parasitol 76:345–351CrossRefGoogle Scholar
- 5.Carroll FI, Blackwell JT (1974) J Med Chem 17:210–219CrossRefGoogle Scholar
- 6.Peters W, Robinson BL, Mittelholzer ML, Crevoisier C, Stürchler D (1995) Ann Trop Med Parasitol 89:465–468Google Scholar
- 7.Ngiam TL, Go ML (1987) Chem Pharm Bull 35:409–412Google Scholar
- 8.Pham YT, Régina A, Farinotti R, Couraud PO, Wainer IW, Roux F, Gimenez F (2000) Biochim Biophys Acta 1524:212–219Google Scholar
- 9.Gimenez F, Farinotti R, Thuillier A, Hazebroucq G, Wainer IW (1990) J Chromatogr 529:339–346CrossRefGoogle Scholar
- 10.Gimenez F, Dumartin C, Wainer IW, Farinotti R (1993) J Chromatogr 619:161–166CrossRefGoogle Scholar
- 11.Bergqvist Y, Al Kabbani J, Pettersson C, Huynh NH (1993) J Chromatogr 620:217–224CrossRefGoogle Scholar
- 12.Bergqvist Y, Doverskog M, Al Kabbani J (1994) J Chromatogr B 652:73–81CrossRefGoogle Scholar
- 13.Wallén L, Ericsson Ö, Wikström I, Hellgren U (1994) J Chromatogr B 655:153–157CrossRefGoogle Scholar
- 14.Hellgren U, Jastrebova J, Jerling M, Krysén B, Bergqvist Y (1996) Eur J Clin Pharmacol 51:171–173CrossRefGoogle Scholar
- 15.Schlagenhauf P, Steffen R, Lobel H, Johnson R, Letz R, Tschopp A, Vranjes N, Bergqvist Y, Ericsson Ö, Hellgren U, Rombo L, Mannino S, Handschin J, Stürchler D (1996) Trop Med Int Health 1:485–494CrossRefGoogle Scholar
- 16.Gimenez F, Pennie RA, Koren G, Crevoisier C, Wainer IW, Farinotti R (1994) J Pharm Sci 83:824–827CrossRefGoogle Scholar
- 17.Martin C, Gimenez F, Bangchang KN, Karbwang J, Wainer IW, Farinotti R (1994) Eur J Clin Pharmacol 47:85–87CrossRefGoogle Scholar
- 18.Bourahla A, Martin C, Gimenez F, Singhasivanon V, Attanath P, Sabchearon A, Chongsuphajaisiddhi T, Farinotti R (1996) Eur J Clin Pharmacol 50:241–244CrossRefGoogle Scholar
- 19.Souri E, Farsam H, Jamali F (1997) J Chromatogr B 700:215–222CrossRefGoogle Scholar
- 20.Baudry S, Pham YT, Baune B, Vidrequin S, Crevoisier C, Gimenez F, Farinotti R (1997) J Pharm Pharmacol 49:1086–1090Google Scholar
- 21.Magalhães IRS, Bonato PS (2008) J Pharm Biomed Anal 46:929–936CrossRefGoogle Scholar
- 22.Berman J (2004) Travel Med Infect Dis 2:171–184CrossRefGoogle Scholar
- 23.Pham YT, Nosten F, Farinotti R, White NJ, Gimenez F (1999) Int J Clin Pharmacol Ther 37:58–61Google Scholar
- 24.Fontaine F, de Sousa G, Burcham PC, Duchêne P, Rahmani R (2000) Life Sci 66:2193–2212CrossRefGoogle Scholar
- 25.Koch M, Blaschke G (1990) Arch Pharm 323:749Google Scholar
- 26.Håkanson A, Landberg-Lindgren A, Björkman A (1990) J Trans R Soc Trop Med Hyg 84:503–504CrossRefGoogle Scholar
- 27.Basco LK, Gillotin C, Gimenez F, Farinotti R, Le Bras J (1991) J Trans R Soc Trop Med Hyg 85:208–209CrossRefGoogle Scholar
- 28.Green MD, Bergqvist Y, Mount DL, Corbett S, D´Souza MJ (1999) J Chromatogr B 727:159–165CrossRefGoogle Scholar
- 29.De Oliveira ARM, Magalhães IRS, De Santana FJM, Bonato PS (2008) Quim Nova 31:637–644Google Scholar
- 30.De Oliveira ARM, Cardoso CD, Bonato PS (2007) Electrophoresis 28:1081–1091CrossRefGoogle Scholar
- 31.Magalhães IRS, Bonato PS (2008) J Sep Sci 31:3106–3116CrossRefGoogle Scholar
- 32.Qiu Y, Kitamura S, Guillory JK (1992) Pharm Res 9:1640–1643CrossRefGoogle Scholar
- 33.Rosing H, Man WY, Doyle E, Bult A, Beijnen JH (2000) J Liq Chrom & Rel Technol 23:329–354CrossRefGoogle Scholar
- 34.Aboul-Enein HY, Ali Y (2002) Il Farmaco 57:513–529CrossRefGoogle Scholar
- 35.Bergqvist Y, Eckerbom S, Larsson N, Churchill FC (1988) J Chromatogr 427:295–305CrossRefGoogle Scholar
- 36.Bergqvist Y, Al Kabbani J, Krysén B, Palme IB, Rombo L (1993) J Chromatogr 615:297–302CrossRefGoogle Scholar
- 37.Ho TS, Pedersen-Bjergaard S, Rasmussen KE (2006) J Chromatogr Sci 44:308–316Google Scholar
- 38.Psillakis E, Kalogerakis N (2003) Trends Anal Chem 22:565–574CrossRefGoogle Scholar
- 39.Rasmussen KE, Pedersen-Bjergaard S (2004) Trends Anal Chem 23:1–10CrossRefGoogle Scholar
- 40.Shah VP, Midha KK, Findlay JWA, Hill HM, Hulse JD, McGilveray IJ, McKay G, Miller KJ, Patnaik RN, Powell ML, Tonelli A, Viswanathan CT, Yacobi A (2000) Pharm Res 17:1551–1557CrossRefGoogle Scholar
