LC–UV/MS quality analytics of paediatric artemether formulations

Vandercruyssen, Kirsten; D׳Hondt, Matthias; Vergote, Valentijn; Jansen, Herwig; Burvenich, Christian; Spiegeleer, Bart De

doi:10.1016/j.jpha.2013.03.006

Cited by 15 publications

(14 citation statements)

References 63 publications

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“…Compounds in the artemisinin family are prone to fragmentation during both electrospray and plasma ionization, and in Supplementary Figure S8c, the characteristic ion fragments for artemether are readily seen at m/z = 163, 221, 267, and 281 as previously identified in the literature [42]. Heating the cross union to 275°C only shifted the relative intensities of the observed species in greater favor of fragments at m/z = 221 and a lesser fragment at m/z = 253 (spectrum not shown), but otherwise did not alter the total ion signal distribution.…”

Section: Tm-vapi Analysis Of Solidssupporting

confidence: 59%

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities

Keelor

Farnsworth

Weber

et al. 2016

J. Am. Soc. Mass Spectrom.

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Abstract. We have developed a multimodal ion source design that can be configured on the fly for various analysis modes, designed for more efficient and reproducible sampling at the mass spectrometer atmospheric pressure (AP) interface in a number of different applications. This vacuum-assisted plasma ionization (VaPI) source features interchangeable transmission mode and laser ablation sampling geometries. Operating in both AC and DC power regimes with similar results, the ion source was optimized for parameters including helium flow rate and gas temperature using transmission mode to analyze volatile standards and drug tablets. Using laser ablation, matrix effects were studied, and the source was used to monitor the products of model prebiotic synthetic reactions.

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Section: Tm-vapi Analysis Of Solidssupporting

confidence: 59%

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities

Keelor

Farnsworth

Weber

et al. 2016

J. Am. Soc. Mass Spectrom.

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“…Impurity profiling of both β-artemether and lumefantrine as well as in-silico toxicity profile of lumefantrine and its related impurities have been reported in previous publications [20,23,28]. Here, in-silico toxicological profile of β-artemether was compared against its related identified impurities using Derek Nexus®.…”

Section: Discussionmentioning

confidence: 90%

“…Previous studies have indicated that AHA-β-artemether is the most critical pair to be separated [28], while other impurities like DKA or furano acetate are sufficiently well separated from β-artemether. Moreover, lumefantrine and its related degradation impurities (DBK and the N-oxide of lumefantrine) were also eluting at different RT.…”

Section: Resultsmentioning

confidence: 99%

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A rapid stability-indicating, fused-core HPLC method for simultaneous determination of β-artemether and lumefantrine in anti-malarial fixed dose combination products

Suleman

Vandercruyssen

Wynendaele

et al. 2013

Malar J

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BackgroundArtemisinin-based fixed dose combination (FDC) products are recommended by World Health Organization (WHO) as a first-line treatment. However, the current artemisinin FDC products, such as β-artemether and lumefantrine, are inherently unstable and require controlled distribution and storage conditions, which are not always available in resource-limited settings. Moreover, quality control is hampered by lack of suitable analytical methods. Thus, there is a need for a rapid and simple, but stability-indicating method for the simultaneous assay of β-artemether and lumefantrine FDC products.MethodsThree reversed-phase fused-core HPLC columns (Halo RP-Amide, Halo C18 and Halo Phenyl-hexyl), all thermostated at 30°C, were evaluated. β-artemether and lumefantrine (unstressed and stressed), and reference-related impurities were injected and chromatographic parameters were assessed. Optimal chromatographic parameters were obtained using Halo RP-Amide column and an isocratic mobile phase composed of acetonitrile and 1mM phosphate buffer pH 3.0 (52:48; V/V) at a flow of 1.0 ml/min and 3 μl injection volume. Quantification was performed at 210 nm and 335 nm for β-artemether and for lumefantrine, respectively. In-silico toxicological evaluation of the related impurities was made using Derek Nexus v2.0®.ResultsBoth β-artemether and lumefantrine were separated from each other as well as from the specified and unspecified related impurities including degradants. A complete chromatographic run only took four minutes. Evaluation of the method, including a Plackett-Burman robustness verification within analytical QbD-principles, and real-life samples showed the method is suitable for quantitative assay purposes of both active pharmaceutical ingredients, with a mean recovery relative standard deviation (± RSD) of 99.7 % (± 0.7%) for β-artemether and 99.7 % (± 0.6%) for lumefantrine. All identified β-artemether-related impurities were predicted in Derek Nexus v2.0® to have toxicity risks similar to β-artemether active pharmaceutical ingredient (API) itself.ConclusionsA rapid, robust, precise and accurate stability-indicating, quantitative fused-core isocratic HPLC method was developed for simultaneous assay of β-artemether and lumefantrine. This method can be applied in the routine regulatory quality control of FDC products. The in-silico toxicological investigation using Derek Nexus® indicated that the overall toxicity risk for β-artemether-related impurities is comparable to that of β-artemether API.

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“…ARM is an official drug used in Indian Pharmacopoeia, British Pharmacopoeia and United State Pharmacopoeia [14][15][16][17][18], whereas LUM is official in USP SALMOUS [18]. Several methods including UV and HPLC, used for the estimation of ARM [19][20][21][22][23][24][25][26][27] while UV, HPLC, HPTLC and tandem techniques used for the estimation of LUM [28][29][30][31][32] have been described in previous literature. However, existing methods involving the simultaneous estimation of ARM and LUM in pharmaceutical dosage form focuses on chromatographic techniques, i.e., HPLC and HPTLC [33][34][35][36][37][38][39][40].…”

Section: Introductionmentioning

confidence: 99%

Optimizing derivatization conditions using an experimental design and simultaneous estimation of artemether and lumefantrine by ratio first order derivative spectrophotometric method

Christian¹,

Shah²,

Patel³

et al. 2017

Journal of Taibah University for Science

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Artemether-lumefantrine is the most widely used artemisinin-based combination therapy for malaria. The present work aims to develop and validate a simple, accurate, precise and rapid ratio first order derivative spectrophotometric method for the simultaneous estimation of artemether and lumefantrine in a fixed dose combination tablet. The first step in development of the method was to derivatize artemether. As artemether does not show absorption in the UV region, it was derivatized using hydrochloric acid as the derivatizing agent. The derivatizing conditions were further optimized by full factorial multivariate approach, where the independent variables were volume of concentrated hydrochloric acid and time taken for artemether derivatization at room temperature. Furthermore, based on the statistical analysis, derivatizing conditions were optimized i.e. 1.3 ml of conc. HCl at room temperature for 30 min. At this condition, the artemether was found to absorb in the UV region satisfactorily, and the absorbance of lumefantrine was found to remain unaffected. The developed method showed good calibration data in the range of 5-30 g/ml for artemether and 2-12 g/ml for lumefantrine. The mean % recovery values were found to be 99.96-100.49% and 99.48-100.31% for artemether and lumefantrine, respectively. Additionally, the developed method was effectively applied in the estimation of artemether and lumefantrine in a commercial tablet (ARH-L DS tablets), suggesting that it can be practically applied for quality control of routinely examined drugs in combined dosage forms with the reduced expenditure of time.

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LC–UV/MS quality analytics of paediatric artemether formulations

Cited by 15 publications

References 63 publications

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities

Multimodal Vacuum-Assisted Plasma Ion (VaPI) Source with Transmission Mode and Laser Ablation Sampling Capabilities

A rapid stability-indicating, fused-core HPLC method for simultaneous determination of β-artemether and lumefantrine in anti-malarial fixed dose combination products

Optimizing derivatization conditions using an experimental design and simultaneous estimation of artemether and lumefantrine by ratio first order derivative spectrophotometric method

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