Development and validation of a headspace gas chromatographic method for the determination of residual solvents in arterolane (RBx11160) maleate bulk drug

Abstract

Objective:Arterolane maleate is an antimalarial drug currently under Phase III clinical evaluation, and presents a simple, economical and scalable synthesis, and does not suffer from safety problems. Arterolane maleate is more active than artemisinin; and is cheap to produce. It has a longer lifetime in the plasma, so it stays active longer in the body. To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. In the current article we are reporting the development and validation of a rapid and specific Head space gas chromatographic (HSGC) method for the determination of organic volatile impurities (residual solvents) in Arterolane Maleate bulk drug.Materials and Methods:The method development and its validation were performed on Perkin Elmer's gas chromatographic system equipped with Flame Ionization detector and head space analyzer. The method involved a thermal gradient elution of ten residual solvents present in arterolane maleate salt in RTx-624, 30 m × 0.32 mm, 1.8 μ column using nitrogen gas as a carrier. The flow rate was 0.5 ml/min and flame ionization detector (FID) was used.Results:During method validation, parameters such as precision, linearity, accuracy, limit of quantification and detection and specificity were evaluated, which remained within acceptable limits.Conclusions:The method has been successfully applied for the quantification of the amount of residual solvents present in arterolane maleate bulk drug.The method presents a simple and reliable solution for the routine quantitative analysis of residual solvents in Arterolane maleate bulk drug.

Development and Validation of a Headspace Gas Chromatographic Method for the Determination of Methyl Bromide Content in Itraconazole API

“…These changes to the genetic material, caused by exposure to very low levels of a genotoxin, can lead to cancer. While ICH published adequate controls for general process-related impurities (Q3A, Q3B), Pharmaceutical Genotoxic impurities (GTI) gained global prominence when regulatory bodies like European Medicines Agency (EMEA) and United States Food and Drug Administration (USFDA) [4,5] some few years back published stringent qualification thresholds lower than the default values set by ICH guidelines. These dictums confirmed that the existing ICH thresholds may not be acceptable for such DNA-reactive genotoxins or carcinogenic impurities.…”

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“…Literature survey reveals Automated Solid Phase Extraction and Liquid Chromatographic Method 3 , Capillary Zone Electrophoresis 4 , HPLC 5 and LC/MS/MS [6][7][8][9][10][11][12] methods for the estimation of Piperaquine phosphate alone or in combination with other drugs in pharmaceutical formulation and biological samples where as headspace gas chromatographic 13 methods for the estimation of Arterolane maleate alone in pharmaceutical formulation and biological samples. There are very few reported methods for the simultaneous determination of Arterolane maleate and Piperaquine phosphate by RP-HPLC in pharmaceutical dosage forms 14,15 .…”

Determination of residual solvents in isobutylboronic acid: Masking derivatization improves stability of GC column

“…The static headspace GC is a conventional and powerful analytical technique that has been adopted and recommended by the European Pharmacopoeia and the United States Pharmacopoeia for the determination of residual solvents within quality control of pharmaceutical products . Relative simplicity of sample preparation, sensitivity and elimination of GC system contamination by unwanted non‐volatile substances belong to the main benefits of the headspace technique . However, analysis of some specific matrices for the RS content requires a special sample pretreatment.…”