A Review on Analytical methods for the determination of Artemether in Pharmaceutical Formulation

Mohan Goud V¹, Deepika S¹, AVSSS Gupta², Sreekanth M³, Linga Kumara Swamy²

¹Dept. of Pharmaceutical Analysis, Hyderabad-500075, Telangana, India.

²Dept. of Pharmacology, Joginpally B.R Pharmacy College, Hyderabad-500075, Telangana, India.

³Research Scholar, JNTUA, Ananthapuramu.

*Corresponding Author E-mail: mohanvanga@yahoo.com

ABSTRACT:

Artemether is a methyl ether derivative of artemisinin. It is antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficiency. Artemether with combination of lumefantrine is the most common artemisinin based combination therapy used in malaria endemic areas. This review article represents the different analytical methods which have been reported for estimation of Artemether in pharmaceutical dosage forms. The Chromatographic methods like, HPLC, RP-HTPLC, RP-HPLC, LC–UV/MS and UV Spectrophotometric method were reported.

KEYWORDS: Artemether, Anti -malarial and Analytical Methods.

1. INTRODUCTION:

Artemether [1-4] is a synthetic derivative of artemisinin. Artemether also called dihydroartemisinin methyl ether, chemically it is[3R,5aS,6R,8aS,9R,10S,12R,12aR]-10-methoxy-3,6,9-trimethyldecahydro-3,12-epoxypyrano [4,3-j]-12-benzodioxepine. It is used to treat infections caused by plasmodium falciparam and unidentified plasmodium species. This drug can be administered as oily solution by intramuscular injection, or tablets.

1.1 Mechanism of action:

Artemether is a methyl ether derivative of artemisinin, which is peroxide containing lactose isolated from the antimalarial plant artemisinin annual. It is a relatively lipophilic and unstable drug, which acts by creating reactive free radicals in addition to affecting the membrane transport system of the plasmodium organism.

2. ANALYTICAL METHOD:

2.1 Compendial Method:

Monograph of Artemether t is not official in any pharmacopoeia, but combination of Artemether and Lumefantrine capsules were discussed in International Pharmacopoeia Monograph.

2.2 Reported Method:

Most of the reported methods for determination of Artemether in pharmaceutical formulations are Liquid chromatographic method. The Reverse Phase chromatography is widely used to determine the assay of Artemether. The summary of reported methods is tabulated below.

Table 1: Summary of chromatography method of Artemether.

Title	Method	Mobile phase	Stationary phase	Wave length
Analytical Method Development & Validation of Artemether in Bulk Drug by RP- HPLC Method as Per ICH Guidelines [5]	RP-HPLC	Acetonitrile and methanol (50:50)	Hypersil ODS C18 (150*4.6 mm), 5 µ	216nm
Development and Validation of a new reverse Phase HPLC method for the determination of Artemether in pharmaceutical dosage form [6]	RP-HPLC	Acetonitrile and acetic acid (0.1% aqueous solution) in the ratio of 85:15	C₁₈column (250 × 4.6mm, 5µm)	216nm
LC–UV/MS quality analytics of paediatric artemether formulations [7]	LC–UV/MS	Prevail organic acid (OA) column (250mm_4.6 mm, 5 μm)	Combined with a linear gradient (where A=25 mM phosphate buffer (pH2.5), and B=acetonitrile) from 30%to75% B	210 nm
Quantitation of artemether in pharmaceutical raw material and injections by high performance liquid chromatography [8]	HPLC	Zorbax C18 column (150 x 4.6 mm; 5 µm)	Acetonitrile and water (70:30)	216 nm
Reversed-Phase Liquid Chromatographic Method for Simultaneous Determination of Artemether and Lumefantrine in Pharmaceutical Preparation [9]	RP-HPLC	methanol: orthophosphoric acid in ratio (80:20 v/v)	Hypersil ODS C18 (250mm×4.6mm×5µ particle Size)	210 nm
Determination of artemether and lumefantrine in anti-malarial fixed-dose combination tablets by microemulsion electrokinetic chromatography with short-end injection procedure [10]	Capillary electrophoretic methods	composed of octane, butanol, sodium dodecyl sulfate and borate buffer	Uncoated fused silica capillary, 30 cm long × 50 μm internal diameter	214 nm
Analysis of active ingredients, Lumefantrine and Artemether in combined antimalarial tablet by HPTLC with densitometric measurement before and after derivatization [11]	HPTLC	toluene: ethyl acetate: acetic acid (2:7.5:0.5, v/v/v)	Silica gel 60 F₂₅₄	269 nm lumefantrine and 519 nm artemether
Development and validation of HPLC-UV method for quantification of artemether in plasma [12]	HPLC-UV	acetonitrile and water in the ratio of 70:30 v/v	Princeton SPHER ODS5 (250 X 4.0 mm; 5 μ)	210 nm
Artemether-Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method [13]	HPLC-LC/MS	ACN and 50 mM potassium dihydrogen orthophosphate buffer (pH 3) in a ratio 55:45	C18 column 100 × 2.1-mm, 3.5-μm	210 nm
Simultaneous Estimation of Artemether and Lumefantrine by RP-HPLC Method development in pharmaceutical tablet dosage form [14]	RP-HPLC	buffer and acetonitrile in the ratio of 50:50v/v	Hypersil BDS C18 ,250 × 4.6 mm, 5 μ	215nm
Analytical Method Development and Validation for Simultaneous Estimation of Artemether and Lumefantrine in Pure and Pharmaceutical Dosage Form Using RP-HPLC Method [15]	RP-HPLC	0.01M tetra butyl ammonium hydrogen sulphate and acetonitrile in the ratio of 20 : 80 (v/v)	BDS Hypersil C18 (150 × 4.6 mm i.d. 3 μm particle size)	222nm
Development and validation of high-performance liquid chromatography-tandem mass spectrometric method for simultaneous determination of Artemether and its metabolite, Dihydroartemisinin in human plasma. A pharmacokinetic study application [16]	HPLC-LC/MS	Acetonitrile: Ammonium formate buffer 2 mM (80:20 v/v)	Polaris A, C18, 50 X 4.6 mm, 5µm column	Detection was made at m/z 316.1 / 267.1 for Artemether

Table 2: UV spectroscopic method

Title

Method

Wavelength

Linearity and r square

Recovery

Validated spectrophotometric method for quantitative determination of Artemether in pharmaceutical formulation [17]

254 nm

5-40 µg/ml

97.93 ± 0.98%

Simultaneous Determination of Artemether and Lumefantrine by Area Under Curve UV Spectrophotometric Method [18]

Artemether

212 nm and Lumefantrine 232nm

Artemether

10 -30µg/ml and Lumefantrine 24 - 44µg/ml

Artemether

100.29 ± 0.88%

Lumefantrine

100.1 ± 0.4%

3. DISCUSSION:

The most widely used method for determination of Artemether was HPLC method. Some various chromatographic conditions are presented in the given above table.

4. CONCLUSION:

The Simple, Specific and Better Separation efficacy made HPLC to be used for Qualitative and Quantitative determination of Artemether. The presented Information is Useful for the future study for researchers involved in quality control and formulation development of Artemether.

5. REFERENCES:

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10. N’Cho Christophe Amin, Huguette Fabre, Marie-Dominique Blanchin, Jérôme Montels and Michele Ake. Determination of artemether and lumefantrine in anti-malarial fixed-dose combination tablets by microemulsion electrokinetic chromatography with short-end injection procedure. Malaria Journal. 2013;12(202):1-21.

11. Meena S and Sandhya M. Analysis of active ingredients, Lumefantrine and Artemether in combined antimalarial tablet by HPTLC with densitometric measurement before and after derivatization. Journal of Liquid Chromatography & Related Technologies. 2014;37 (10):1416-24.

12. Vaishali Yogesh Jadhav and Kamalinder Singh. Development and validation of HPLC-UV method for quantification of artemether in plasma. Journal of Pharmacognosy and Phytochemistry. 2018; SP6:75-8.

13. Philip Debrah, Henry Nettey, Katja Kjeldgaard Miltersen, Patrick Ayeh-Kumi, Birgitte Brock, Joseph Adusei Sarkodie et al. Artemether-Lumefantrine Concentrations in Tablets and Powders from Ghana Measured by a New High-Performance Liquid Chromatography Method. Am J Trop Med Hyg. 2016 Jul 6;95(1):158–63.

14. 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 Erud. 2013;3(1):10-7.

15. Vinodh M, Vinayak M, Pankaj P, Rahul K, Renita M. Analyticalmethod development and validation for simultaneousestimation of Artemether and Lumefantrine in pure and pharmaceutical dosage form using RP HPLC method. Malay JAnal Sci. 2013;17(3):348–58.

16. Terish JD, Suresh Kumar, Ramesh N, Sasi jith SL. Development and validation of high-performance liquid chromatography-tandem mass spectrometric method for simultaneous determination of Artemether and its metabolite, Dihydroartemisinin in human plasma. A pharmacokinetic study application. Eur J Exp Biol. 2011;1(3):169-79.

17. Pratap YP, Manisha CP, Geetanjali KG, Manish AR, Harshada PB. Validated spectrophotometric method for quantitative determination of Artemether in pharmaceutical formulation. Der Pharma Chemica. 2011;3(3):135-39.

18. Karajgi SR, Tanveer AR and Kalyane NV. Simultaneous Determination of Artemether and Lumefantrine by Area under Curve UV Spectrophotometric Method. J. Pharm. Sci. & Res. 2016;8(6):506-11.

Received on 07.02.2020 Modified on 05.03.2020

Asian J. Pharm. Ana. 2020; 10(2):112-114.

DOI: 10.5958/2231-5675.2020.00020.4