Abstract:A simple, rapid, precise, and accurate UV-visible spectrophotometric method has been developed for the simultaneous determination of Artesunate in combination with Me�oquine. For developing the method, methanol was used as a solvent. Artesunate and Me�oquine showed max at 240 nm and 222 nm, respectively. e proposed method was validated as per ICH guideline. e linearity range of Artesunate and Me�oquine were 10-60 and 20-120 g/mL, respectively. 99.91 ± 0.2740 and 99.56 ± 0.2067 these value represent the perce… Show more
“…UV spectrum of artesunate in methanol at 50 μg/ml concentration showed UV max at 225 nm as compared to reported 240 nm ( Fig. 1 ) in Kalyankar et al [21] . In Fig.…”
Section: Resultssupporting
confidence: 57%
“… Fig. 1 UV spectrum of artesunate sample in methanol at 50 μg/ml concentration screened at 220–240 nm showed UV max 225 nm as compared to 240 nm reported in Kalyankar et al [21] . Fig.…”
Section: Resultsmentioning
confidence: 64%
“…A simple, rapid, precise and accurate UV–vis spectrophotometric method developed by Kalyankar et al [21] has been used for screening UV max of artesunate. Accurately weighed quantity of artesunate was dissolved in methanol to get the concentration of 50 mg/ml.…”
Artesunate is a potent and rapidly acting blood schizontocide used to treat chloroquine resistant malaria. Artesunate has been reported to cause embryo, reduced reproductive capacity, hepatotoxicity, neurotoxicity and hematological abnormalities. Previously toxicity studies on artesunate have been done in 2–10 mg/kg dose range mostly for 7 days, scientific studies on sub-chronic exposure of artesunate is not been reported so for. The present study evaluates sub-chronic safety profile of artesunate on 45 days oral administration at 2, 4 and 8 mg/kg/day. Authentication of artesunate has been done by color test, pH, melting point, loss on drying, UVmax, TLC and HPLC study. Artesunate has non-significant effect on liver and kidney weight. Serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphate (ALP), cholesterol (TC), triglyceride (TG), total protein, albumin, bilirubin, creatinine, urea and glucose content were estimated after 45 days treatment along with hematological screening. Artesunate treatment for 45 days significantly increased (p < 0.05–0.001) SGOT, SGPT, ALP, TC, TG, total bilirubin, glucose level at 8 mg/kg/day dose. It has non-significant effect on serum total protein, albumin, creatinine and urea. Hemoglobin, total RBC, platelet, lymphocytes, basophil, mean cell volume and mean corpuscular hemoglobin concentration have not changed but total WBC, neutrophil, eosinophil, packed cell volume and mean cell hemoglobin were increased significantly (p < 0.01) at 8 mg/kg/day dose. Artesunate treatment at 4 and 8 mg/kg/day showed sinusoidal dilation, cytoplasmic vaculation, focal necrosis, sinusoidal congestion and extensive inflammatory changes, whereas kidney was free of any deleterious effect.ConclusionSub-chronic exposure of artesunate at 8 mg/kg/day dose for 45 days period cause hepatic damage along with hematological abnormalities signifying safety concern.
“…UV spectrum of artesunate in methanol at 50 μg/ml concentration showed UV max at 225 nm as compared to reported 240 nm ( Fig. 1 ) in Kalyankar et al [21] . In Fig.…”
Section: Resultssupporting
confidence: 57%
“… Fig. 1 UV spectrum of artesunate sample in methanol at 50 μg/ml concentration screened at 220–240 nm showed UV max 225 nm as compared to 240 nm reported in Kalyankar et al [21] . Fig.…”
Section: Resultsmentioning
confidence: 64%
“…A simple, rapid, precise and accurate UV–vis spectrophotometric method developed by Kalyankar et al [21] has been used for screening UV max of artesunate. Accurately weighed quantity of artesunate was dissolved in methanol to get the concentration of 50 mg/ml.…”
Artesunate is a potent and rapidly acting blood schizontocide used to treat chloroquine resistant malaria. Artesunate has been reported to cause embryo, reduced reproductive capacity, hepatotoxicity, neurotoxicity and hematological abnormalities. Previously toxicity studies on artesunate have been done in 2–10 mg/kg dose range mostly for 7 days, scientific studies on sub-chronic exposure of artesunate is not been reported so for. The present study evaluates sub-chronic safety profile of artesunate on 45 days oral administration at 2, 4 and 8 mg/kg/day. Authentication of artesunate has been done by color test, pH, melting point, loss on drying, UVmax, TLC and HPLC study. Artesunate has non-significant effect on liver and kidney weight. Serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphate (ALP), cholesterol (TC), triglyceride (TG), total protein, albumin, bilirubin, creatinine, urea and glucose content were estimated after 45 days treatment along with hematological screening. Artesunate treatment for 45 days significantly increased (p < 0.05–0.001) SGOT, SGPT, ALP, TC, TG, total bilirubin, glucose level at 8 mg/kg/day dose. It has non-significant effect on serum total protein, albumin, creatinine and urea. Hemoglobin, total RBC, platelet, lymphocytes, basophil, mean cell volume and mean corpuscular hemoglobin concentration have not changed but total WBC, neutrophil, eosinophil, packed cell volume and mean cell hemoglobin were increased significantly (p < 0.01) at 8 mg/kg/day dose. Artesunate treatment at 4 and 8 mg/kg/day showed sinusoidal dilation, cytoplasmic vaculation, focal necrosis, sinusoidal congestion and extensive inflammatory changes, whereas kidney was free of any deleterious effect.ConclusionSub-chronic exposure of artesunate at 8 mg/kg/day dose for 45 days period cause hepatic damage along with hematological abnormalities signifying safety concern.
“…Several methods for the simultaneous quantification these drugs can be found in the literature, such as ultraviolet (UV) spectrophotometry [ 10 , 11 ], high performance liquid chromatography (HPLC) with UV spectrophotometry detection [ 12 , 13 ], high performance thin layer chromatography (HPTLC) with UV spectrophotometry detection [ 13 , 14 ], and HPLC coupled with tandem mass spectroscopy (HPLC–MS/MS) [ 15 ]. Despite being very commonly used, no methods for quality control of available products are described in the pharmacopoeias [ 16 – 19 ].…”
BackgroundMalaria is one of the most lethal and life-threatening infectious diseases in the world, causing more than half a million deaths annually. Treatment with mefloquine and artesunate is currently recommended by the World Health Organization, and was historically the first artemisinin-based combination therapy used clinically for treatment of Plasmodium falciparum. The problem of poor-quality medicines, such as counterfeit and sub-standard anti-malarials, is a worldwide issue; therefore, it is essential to develop rapid, low cost, solvent-free, and reliable methods for routine quality control for these drugs. The aim of this study was to develop and validate a novel multivariate method for direct simultaneous quantification of mefloquine and artesunate in tablets by diffuse reflectance, middle infrared spectroscopy and partial least squares regression (MIR-PLS).MethodsDiffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and partial least squares regression were applied for simultaneous quantification of artesunate and mefloquine in tablets provided by the Brazilian Government. The model was obtained with full spectra (4000–400 cm−1) preprocessed by first derivative and Savitzky-Golay smoothing followed by mean centring, and built with three latent variables. The method was validated according to Brazilian and international guidelines through the measuring of figures of merit, such as trueness, precision, linearity, analytical sensitivity, selectivity, bias, and residual prediction deviation. The results were compared to an HPLC–MS/MS method.ResultsThe MIR-PLS method provided root mean square errors of prediction lower than 2.0 mg per 100 mg of powder for the two analytes, and proved to be valid according to guidelines for analytical methods that use infrared (IR) spectroscopy with multivariate calibration. For the samples obtained from Brazilian healthcare units, the method provided results statistically similar to those obtained by HPLC–MS/MS.ConclusionMIR-PLS was found to be suitable for the quality control of these drugs. It is fast, does not use solvents, and does not generate chemical waste. Furthermore, the proposed method may be transferred and developed for use in portable equipment, increasing the possibilities for assessing the quality of these drugs.
“…8 The design of analytical methods for quality control of pharmaceutical products should be an important research objective to ensure public health improvement. Despite the frequent use of fixed-dose combination tablets of ARS and MFQ, no method for their quality control has been described in the pharmacopoeias.9-12 Few methods for the simultaneous quantification of drugs in pharmaceutical formulations have been published and include UV spectrophotometry, 13,14 high-performance liquid chromatography (HPLC) with UV spectrophotometry detection, 15,16 and high-performance thin layer chromatography (HPTLC) with UV spectrophotometry detection. 16,17 UV spectrophotometry is a simple and cost-effective analytical method; however, the presence of complex mixtures limits its use owing to the low specificity of the technique.…”
We developed and validated a liquid chromatography tandem mass spectrometry (LC-MS/MS) method to quantify the antimalarials artesunate (ARS) and mefloquine (MFQ) in fixed-dose tablets. The detection was performed by a triple-quadrupole mass spectrometer in multiple reaction monitoring (MRM) in positive ion mode via electrospray ionization. Chromatographic separation was achieved with an XBridge C18 column (50 × 2.1 mm, 5 μm), using isocratic elution (350 μL min -1 ) of water/acetonitrile/methanol (30:35:35, v/v/v) containing 0.1% formic acid. The method was validated according to the International Conference of Harmonization (ICH) guidelines. The calibration curves obtained for ARS (400 to 600 ng mL -1 ) and MFQ (800 to 1200 ng mL -1 ) showed good linearity (r 2 > 0.99), precision (relative standard deviation (RSD): ARS < 2.0%; MFQ < 1.9%), and accuracy (recoveries: ARS, 102.4-103.4%; MFQ, 97.4-101.6%), and were stable for 24 h at 8 °C. The method was successfully applied to commercial tablets, and recoveries of 98.7 ± 4.7% (ARS) and 105.6 ± 3.13% (MFQ). The method developed is a reliable alternative for public quality inspection control with the advantage of tandem mass specificity and speed.
Keywords: antimalarial, artesunate, LC-MS/MS, mefloquine, validation
IntroductionMalaria is an infectious disease caused by protozoan parasites of the genus Plasmodium.1 Several Plasmodium species are known to infect humans, and Plasmodium falciparum is considered the most dangerous species, since it is responsible for the most severe and fatal cases of malaria.2 Malaria is one of the most serious public health concerns worldwide and 3.2 billion people remain at risk of being infected. In 2015, 214 million new cases of malaria and 438,000 deaths were reported. 2 The treatment of malaria is based on targeting the lifecycle of the parasite. The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs), such as artesunate (ARS) (C 19 (Figure 1), for the treatment of uncomplicated malaria, caused by P. falciparum.
2,3ACTs combine two active drugs with different mechanisms of action in order to increase the spectrum of activity and effectiveness, and to prevent antimalarial drug resistance. In an ACT, the immediate effect of an artemisinin derivative, which rapidly clears asexual blood-stage parasites and gametocytes, is combined with J. Braz. Chem. Soc. 616 a drug of a different class that has a longer half-life, thus eliminating residual parasites. 4,5 One of the barriers in the fight against malaria is the increasing presence on the market of counterfeit drugs, which, in recent years, has led to the development of P. falciparum resistance to therapy.
Simultaneous Determination of Antimalarial Agents by LC-MS/MS and Its Application6 Antimalarials are among the most widely administered drugs in tropical countries and have been particularly targeted by counterfeiters. The use of counterfeit drugs or substandard antimalarial drugs can cause increased morbidity, adverse effects, and mortal...
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