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

Gupta A, Singh Y, Srinivas KS, Jain G, Sreekumar VB, Semwal VP - J Pharm Bioallied Sci (2010)

Bottom Line: 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.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 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.

Affiliation: Analytical Research and Development-New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana-122 001, India.

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.

Structure of arterolane maleate
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Figure 1: Structure of arterolane maleate

Mentions: Arterolane maleate [Figure 1] 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.[8] Arterolane maleate contains a type of bridge that is considered important for its activity (it generates radicals that target proteins in the parasite), and was engineered with the bulky adamantane group next to it to protect the peroxide bridge.[9] Arterolane maleate is more active than artemisinin; it has sufficient solubility to be administered orally, and is cheap to produce. It has a longer lifetime in the plasma, so it stays active longer in the body.[10–12] To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. HSGC is one of the most widely accepted techniques used to monitor the residual solvents present in APIs. Therefore, a highly selective, rapid and linear HSGC method was developed for the quantification of a total of 10 residual solvents which are used during the synthesis and manufacturing of arterolane maleate in accordance with International Conference on Harmonization (ICH) guidelines.[1314]

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

Gupta A, Singh Y, Srinivas KS, Jain G, Sreekumar VB, Semwal VP - J Pharm Bioallied Sci (2010)

Structure of arterolane maleate
© Copyright Policy
Figure 1: Structure of arterolane maleate
Mentions: Arterolane maleate [Figure 1] 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.[8] Arterolane maleate contains a type of bridge that is considered important for its activity (it generates radicals that target proteins in the parasite), and was engineered with the bulky adamantane group next to it to protect the peroxide bridge.[9] Arterolane maleate is more active than artemisinin; it has sufficient solubility to be administered orally, and is cheap to produce. It has a longer lifetime in the plasma, so it stays active longer in the body.[10–12] To provide quality control over the manufacture of any API, it is essential to develop highly selective analytical methods. HSGC is one of the most widely accepted techniques used to monitor the residual solvents present in APIs. Therefore, a highly selective, rapid and linear HSGC method was developed for the quantification of a total of 10 residual solvents which are used during the synthesis and manufacturing of arterolane maleate in accordance with International Conference on Harmonization (ICH) guidelines.[1314]

Bottom Line: 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.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 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.

Affiliation: Analytical Research and Development-New Drug Discovery Research, Ranbaxy Research Laboratories, Gurgaon, Haryana-122 001, India.

ABSTRACT

Background:

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.

View Similar Images In: Results  - Collection
View Article: Pubmed Central -  PubMed
Show All Figures - Show MeSH
getmorefigures.php?pmc=3146089&rFormat=json&query=null&req=5