A selective LC-MS/MS method for simultaneous quantification of Artemether, Lumefantrine and their principle metabolites in human plasma
DOI:
https://doi.org/10.18034/ra.v6i3.335Keywords:
Artemether, Lumefantrine, Metabolites, LC-MS/MS, Pharmacokinetics, Human plasmaAbstract
We have developed and validated a sensitive, selective and reproducible reversed-phase high-performance liquid chromatography method coupled with electrospray ionization mass spectrometry (HPLC–ESI-MS/MS) for the simultaneous quantitation of artemether (ART), dihydroartemisinin (DHA), lumefantrine (LUM) and desbutyl-lumefantrine (DBL) in human plasma. Mefloquine was used as an internal standard (IS). The analytes were extracted by protein precipitation procedure and separated on a reversed-phase Zorbax SB-Ciano column with a mobile phase composed of acetonitrile and 20mM aqueous ammonium formate containing 0.5% (v/v) formic acid. Multiple reaction monitoring was performed in the positive ion mode using the transitions m/z 316.3→m/z 163.1 (ART), m/z 302.3→m/z 163.1 (DHA), m/z 530.3→m/z 512.2. (LUM), m/z 472.2→m/z 454.1 (DBL) and m/z 379.1→m/z 361.1(MQ) to quantify the drugs. Calibration curves in spiked plasma were linear (r2 ≥ 0.9992) over the range of 5–1500 ng/mL for ART/ DHA and 5–5,000 ng/mL for LUM/DBL. The lower limit of quantitation (LLOQ) was 10 ng/mL ART/ DHA and 5 ng/mL for LUM/ DBL. The mean R.S.D. values for the intra-run precision were 2.2% , 3.8%, 1.9% and 4.7% and for the inter-run precision were 3.2%, 3.6% , 4.4% and 3.5% for ART, DHA, LUM and DBL, respectively. The mean percentage recovery values were 93.2%, 98.5%, 97.1% and 99.4% for ART, DHA, LUM and DBL, respectively. No matrix effect was detected for all the analytes and the IS. The validated method was successfully applied to determine the plasma concentrations of ART, DHA, LUM and DBL in pregnant and non-pregnant women volunteers in a multiple-dose pharmacokinetics study over the course of 336 hours.
Downloads
References
Annerberg, A., et al. (2005), “High Throughput Assay for the Determination of Lumefantrine in Plasma.” Journal of Chromatography B, vol. 822, no. 1–2, pp. 330–33. Crossref, doi:10.1016/j.jchromb.2005.06.022.
Ashley, Elizabeth A., et al. (2007), “Pharmacokinetic Study of Artemether-Lumefantrine given Once Daily for the Treatment of Uncomplicated Multidrug-Resistant Falciparum Malaria: Once-Daily Artemether-Lumefantrine to Treat Falciparum Malaria.” Tropical Medicine & International Health, vol. 12, no. 2, pp. 201–08. Crossref, doi:10.1111/j.1365-3156.2006.01785.x.
César, Isabela da Costa, et al. (2008), “Simultaneous Determination of Artemether and Lumefantrine in Fixed Dose Combination Tablets by HPLC with UV Detection.” Journal of Pharmaceutical and Biomedical Analysis, vol. 48, no. 3, pp. 951–54. Crossref, doi:10.1016/j.jpba.2008.05.022.
Ezzet, F., et al. (2000), “Pharmacokinetics and Pharmacodynamics of Lumefantrine (Benflumetol) in Acute Falciparum Malaria.” Antimicrobial Agents and Chemotherapy, vol. 44, no. 3, pp. 697–704. Crossref, doi:10.1128/AAC.44.3.697-704.2000.
Global Report on Antimalarial Drug Efficacy and Drug Resistance: 2000-2010. World Health Organization, 2010.Open World Cat, http://whqlibdoc.who.int/publications/2010/9789241500470_eng.pdf.
Hodel, E. M., et al. (2009), “A Single LC–Tandem Mass Spectrometry Method for the Simultaneous Determination of 14 Antimalarial Drugs and Their Metabolites in Human Plasma.” Journal of Chromatography B, vol. 877, no. 10, pp. 867–86. Crossref, doi:10.1016/j.jchromb.2009.02.006.
Karbwang, J., et al. (1997), “Determination of Artemether and Its Major Metabolite, Dihydroartemisinin, in Plasma Using High-Performance Liquid Chromatography with Electrochemical Detection.” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 690, no. 1–2, pp. 259–65. Crossref, doi:10.1016/S0378-4347(96)00422-7.
Karbwang, J., et al. (1997), “Pharmacokinetics and Bioavailability of Oral and Intramuscular Artemether.” European Journal of Clinical Pharmacology, vol. 52, no. 4, pp. 307–10. Crossref, doi:10.1007/s002280050295.
Khuda, Fazli, et al. (2016), “A High-Resolution LC–MS/MS Method for the Quantitative Determination of Artemether and Its Metabolite Dihydroartemisinin in Human Plasma and Its Application to Pharmacokinetic Studies.” Chromatographia, vol. 79, no. 9–10, pp. 609–18. Crossref, doi:10.1007/s10337-016-3064-6.
Lindegårdh, N., et al. (2005), “Development and Validation of a Bioanalytical Method Using Automated Solid-Phase Extraction and LC-UV for the Simultaneous Determination of Lumefantrine and Its Desbutyl Metabolite in Plasma.” Journal of Pharmaceutical and Biomedical Analysis, vol. 37, no. 5, pp. 1081–88. Crossref, doi:10.1016/j.jpba.2004.07.041.
Mansor, Sharif M., et al. (1996), “Determination of a New Antimalarial Drug, Benflumetol, in Blood Plasma by High-Performance Liquid Chromatography.” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 682, no. 2, pp. 321–25. Crossref, doi:10.1016/0378-4347(96)00086-2.
Martensson, A., et al. (2005), “Efficacy of Artesunate Plus Amodiaquine versus That of Artemether-Lumefantrine for the Treatment of Uncomplicated Childhood Plasmodium Falciparum Malaria in Zanzibar, Tanzania.” Clinical Infectious Diseases, vol. 41, no. 8, pp. 1079–86. Crossref, doi:10.1086/444460.
McGready, Rose, et al. (2006), “The Pharmacokinetics of Artemether and Lumefantrine in Pregnant Women with Uncomplicated Falciparum Malaria.” European Journal of Clinical Pharmacology, vol. 62, no. 12, pp. 1021–31. Crossref, doi:10.1007/s00228-006-0199-7.
Mugoyela, Veronica, and Omary Minzi. (2011), “Implementation of Artemether-Lumefantrine Treatment Policy for Malaria at Health Facilities in Tanzania.” Risk Management and Healthcare Policy, p. 89. Crossref, doi:10.2147/RMHP.S23054.
Navaratnam, V., et al. (1995), “Determination of Artemether and Dihydroartemisinin in Blood Plasma by High-Performance Liquid Chromatography for Application in Clinical Pharmacological Studies.” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 669, no. 2, pp. 289–94. Crossref, doi:10.1016/0378-4347(94)00109-I.
Omari, Aika A., et al. (2004), “Artemether-Lumefantrine for Uncomplicated Malaria: A Systematic Review.” Tropical Medicine and International Health, vol. 9, no. 2, pp. 192–99. Crossref, doi:10.1046/j.1365-3156.2003.01186.x.
Sabarinath, S., et al. (2003), “A Sensitive and Selective Liquid Chromatographic/Electrospray Ionization Tandem Mass Spectrometric Assay for the Simultaneous Quantification of ?-,?-Arteether and Its Metabolite Dihydroartemisinin in Plasma, Useful for Pharmacokinetic Studies.” Journal of Mass Spectrometry, vol. 38, no. 7, pp. 732–42. Crossref, doi:10.1002/jms.487.
Sandrenan, N., et al. (1997), “Determination of Artemether and Its Metabolite, Dihydroartemisinin, in Plasma by High-Performance Liquid Chromatography and Electrochemical Detection in the Reductive Mode.” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 691, no. 1, pp. 145–53. Crossref, doi:10.1016/S0378-4347(96)00431-8.
Shi, Bin, et al. (2006), “Quantitative Analysis of Artemether and Its Metabolite Dihydroartemisinin in Human Plasma by LC with Tandem Mass Spectrometry.” Chromatographia, vol. 64, no. 9–10, pp. 523–30. Crossref, doi:10.1365/s10337-006-0064-y.
Souppart, C., et al. (2002), “Development and Validation of a High-Performance Liquid Chromatography–Mass Spectrometry Assay for the Determination of Artemether and Its Metabolite Dihydroartemisinin in Human Plasma.” Journal of Chromatography B, vol. 774, no. 2, pp. 195–203. Crossref, doi:10.1016/S1570-0232(02)00207-6.
Van, A., Peter, et al. (2013), “The European Bioanalysis Forum Community’s Evaluation, Interpretation and Implementation of the European Medicines Agency Guideline on Bioanalytical Method Validation.” Bioanalysis, vol. 5, no. 6, pp. 645–59. Crossref, doi:10.4155/bio.13.19.
Wahajuddin, et al. (2009), “Determination of Lumefantrine in Rat Plasma by Liquid–Liquid Extraction Using LC–MS/MS with Electrospray Ionization: Assay Development, Validation and Application to a Pharmacokinetic Study.” Journal of Chromatography B, vol. 877, no. 11–12, pp. 1133–39. Crossref, doi:10.1016/j.jchromb.2009.02.058.
White, Nicholas J., et al. (1999), “Clinical Pharmacokinetics and Pharmacodynamics of Artemether-Lumefantrine:” Clinical Pharmacokinetics, vol. 37, no. 2, pp. 105–25. Crossref, doi:10.2165/00003088-199937020-00002.
Xing, Jie, et al. (2006), “A High-Performance Liquid Chromatography/Tandem Mass Spectrometry Method for the Determination of Artemisinin in Rat Plasma.” Rapid Communications in Mass Spectrometry, vol. 20, no. 9, pp. 1463–68. Crossref, doi:10.1002/rcm.2467.
Zeng, Mei-Yi, et al. (1996), “Determination of Benflumetol in Human Plasma by Reversed-Phase High-Performance Liquid Chromatography with Ultraviolet Detection.” Journal of Chromatography B: Biomedical Sciences and Applications, vol. 681, no. 2, pp. 299–306. Crossref, doi:10.1016/0378-4347(95)00542-0.
--0--
Downloads
Published
Issue
Section
License
ABC Research Alert is an Open Access journal. Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal the right of first publication with the work simultaneously licensed under a CC BY-NC 4.0 International License that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of their work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal. We require authors to inform us of any instances of re-publication.
