VALIDATED REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD FOR THE SIMULTANEOUS DETERMINATION OF ARTEMETHER AND LUMEFANTRINE IN FIXED COMBINED DOSAGE FORM

  • Payyavula Venkata Rao
  • Rambabu C

Abstract

ABSTRACT
Objective: The present aim is to develop simple, precise, and accurate reverse phase high performance liquid chromatographic method (RP-HPLC) for
the simultaneous assay of artemether and lumefantrine in fixed combined dosage form.
Methods: The chromatographic study was carried out on Hypersil C18 column (250×4.6 mm, 5 μ) with mobile phase containing a mixture of KH2PO4
buffer (pH-3.5) and acetonitrile in the ratio of 45:55% v/v at a flow rate of 1.0 ml/minute with ultraviolet detection at 218 nm in ambient column
temperature.
Results: Using the optimized chromatographic conditions artemether and lumefantrine eluted with retention times of 2.207 and 3.733 minutes,
respectively. The method was validated according to ICH guidelines with good reproducibility and linear responses, y=60.813.x+629.53 (r²=0.9982)
for artemether and y=88.3108.x+2370.2 (r²=0.9912). The % relative standard deviations of intra-day precision was ranged 0.378% and 1.26% for
artemether and 0.459% and 1.15% for lumefantrine, respectively. The percentage recoveries were ranged from 99.96% to 100.02% for artemether
and 99.96-99.97% for lumefantrine, respectively.
Conclusions: The developed RP-HPLC method was validated as per ICH guidelines and was found to be best suitable for pharmacokinetic studies of
these mentioned drugs.
Keywords: Artemether, Lumefantrine, ICH guidelines.

References

REFERENCES
1. Haynes RK, Vonwiller SC. Extraction of artemisinin and artemisinic acid: Preparation of artemether and new analogues. Trans R Soc Trop Med Hyg 1994;88 Suppl 1:S23-6.
2. Sweetman SC. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009. p. 598-9.
3. Sweetman SC. Martindale: The Complete Drug Reference. 36th ed. London: Pharmaceutical Press; 2009. p. 605.
4. Makanga M, Krudsood S. The clinical efficacy of artemether/lumefantrine (Coartem). Malar J 2009;8 Suppl 1:S5.
5. Mutabingwa TK, Adam I. Use of artemether-lumefantrine to treat malaria during pregnancy: What do we know and need to know? Expert Rev Anti Infect Ther 2013;11(2):125-35.
6. César Ida C, Andrade Nogueira FH, Antônio Pianetti G. Simultaneous determination of artemether and lumefantrine in fixed dose combination tablets by HPLC with UV detection. J Pharm Biomed Anal 2008;48(3):951-4.
7. Huang L, Lizak PS, Jayewardene AL, Marzan F, Lee MN, Aweeka FT. A modified method for determination of lumefantrine in human plasma by HPLC-UV and combination of protein precipitation and solid-phase extraction: Application to a pharmacokinetic study. Anal Chem Insights 2010;5:15-23.
8. Kalyankar TM, Kakde RB. Reversed-phase liquid chromatographic method for simultaneous determination of artemether and lumefantrine in pharmaceutical preparation. Int J ChemTech Res 2011;3(3):1722-7.
9. Suleman S, Vandercruyssen K, Wynendaele E, D’Hondt M, Bracke N, Duchateau L, et al. A rapid stability-indicating, fused-core HPLC method for simultaneous determination of ß-artemether and lumefantrine in anti-
Table 6: Results of robustness studies of artemether and lumefantrine
Chromatographic parameters
Changed value
Retention time
Tailing factor
Artemether
Lumefantrine
Artemether
Lumefantrine
Flow rate (ml/minute)
0.8
2.930
4.907
1.444
1.308
1.2
1.780
2.980
1.368
1.185
Wavelength (nm)
216
2.223
3.710
1.36
1.219
220
2.203
3.207
1.409
1.219
Table 7: Stability data of artemether and lumefantrine
Drug
% Assay at 0 hr*
% Assay at 24 hrs*
% Deviation*
Artemether
99.40
99.94
0.99
Lumefantrine
99.91
99.98
0.99
*Average of six determinations
Fig. 4: Calibration curve of artemether
Fig. 5: Calibration curve of lumefantrine
Table 8: Results for analysis in formulations
Sample No. Combither
Peak area
Artemether 20 mg
Lumefantrine 120 mg
1
99.95
99.97
2
99.84
100.05
3
99.57
99.94
Average*
99.78
99.98
SD*
0.1955
0.0568
%RSD*
0.195
0.0568
*Average of three determinations. RSD: Relative standard deviation,
SD: Standard deviation
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Rao and Rambabu
malarial fixed dose combination products. Malar J 2013;12:145.
10. Gupta NK, Babu AM, Gupta P. Simultaneous estimation of artemether and lumefantrine by RP-HPLC method development in pharmaceutical tablet dosage form. Int J Pharm Erudition 2013;3(1):10-7.
11. Gaikwad S, Tajne M, Gaikwad N, Daud A, Lonare D, Lonare M. HPLC method development and validation for simultaneous estimation of antimalarial drugs artemether and lumefantrine. Int J Pharm Sci Health Care 2016;6:24-31.
12. ICH Harmonized Tripartite Guideline International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use. Validation of Analytical Procedures: Text and Methodolgy; 2005.
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Venkata Rao, P., and R. C. “VALIDATED REVERSE PHASE HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD FOR THE SIMULTANEOUS DETERMINATION OF ARTEMETHER AND LUMEFANTRINE IN FIXED COMBINED DOSAGE FORM”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 10, no. 3, Mar. 2017, pp. 159-63, doi:10.22159/ajpcr.2017.v10i3.15930.
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