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Reversed-phase fused-core HPLC modeling of peptides.

ABSTRACT: Different fused-core stationary phase chemistries (C18, Amide, Phenyl-hexyl and Peptide ES-C18) were used for the analysis of 21 structurally representative model peptides. In addition, the effects of the mobile phase composition (ACN or MeOH as organic modifier; formic acid or acetic acid, as acidifying component) on the column selectivity, peak shape and overall chromatographic performance were evaluated. The RP-amide column, combined with a formic acid-acetonitrile based gradient system, performed as best. A peptide reversed-phase retention model is proposed, consisting of 5 variables: log SumAA, log Sv, clog P, log nHDon and log nHAcc. Quantitative structure-retention relationship (QSRR) models were constructed for 16 different chromatographic systems. The accuracy of this peptide retention model was demonstrated by the comparison between predicted and experimentally obtained retention times, explaining on average 86% of the variability. Moreover, using an external set of 5 validation peptides, the predictive power of the model was also demonstrated. This peptide retention model includes the novel in-silico calculated amino acid descriptor, AA, which was calculated from log P, 3D-MoRSE, RDF and WHIM descriptors.

SUBMITTER: D'Hondt M

PROVIDER: S-EPMC5760978 | biostudies-literature | 2013 Apr

REPOSITORIES: biostudies-literature

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Reversed-phase fused-core HPLC modeling of peptides.

D'Hondt Matthias M Gevaert Bert B Stalmans Sofie S Van Dorpe Sylvia S Wynendaele Evelien E Peremans Kathelijne K Burvenich Christian C De Spiegeleer Bart B

Journal of pharmaceutical analysis 20121130 2

Different fused-core stationary phase chemistries (C18, Amide, Phenyl-hexyl and Peptide ES-C18) were used for the analysis of 21 structurally representative model peptides. In addition, the effects of the mobile phase composition (ACN or MeOH as organic modifier; formic acid or acetic acid, as acidifying component) on the column selectivity, peak shape and overall chromatographic performance were evaluated. The RP-amide column, combined with a formic acid-acetonitrile based gradient system, perf ...[more]

PMID: 29403802

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Project description: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 ?-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 ?-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. ?-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 1 mM phosphate buffer pH 3.0 (52:48; V/V) at a flow of 1.0 ml/min and 3 ?l injection volume. Quantification was performed at 210 nm and 335 nm for ?-artemether and for lumefantrine, respectively. In-silico toxicological evaluation of the related impurities was made using Derek Nexus v2.0®.ResultsBoth ?-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 ?-artemether and 99.7 % (± 0.6%) for lumefantrine. All identified ?-artemether-related impurities were predicted in Derek Nexus v2.0® to have toxicity risks similar to ?-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 ?-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 ?-artemether-related impurities is comparable to that of ?-artemether API.

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Reversed-phase fused-core HPLC modeling of peptides.

Publications

Reversed-phase fused-core HPLC modeling of peptides.

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