Temozolomide is an antineoplastic drug used orally to treat some brain tumors such as glioblastoma multiforme and malignant glioma which has not responded to first-line chemotherapy. The principal hydrolysis product of temozolomide is Impurity A (Figure 1). This compound is poorly retained by reversed-phase (RP) HPLC; compendial methods employ an ion pair reagent (5 mM sodium 1-hexanesulfonate) to achieve adequate retention. Depending on the drug product matrix, ion-pair HPLC can exhibit poor robustness and ANP chromatography was evaluated as an alternative.<br/><br/>A Cogent Diamond Hydride column and an isocratic mobile phase comprising different proportions of water and acetonitrile, acidified with 0.1 % acetic acid was used for the study. Impurity A was well retained at high acetonitrile concentrations (ANP conditions). At lower acetonitrile concentrations (RP conditions), the retention of a different impurity (Impurity C) improved. Retention time data under ANP conditions are shown in Table 1. Retention mechanisms under ANP and RP conditions are discussed.

Retention behavior of temozolomide and its impurities under reversed phase and aqueous normal phase conditions

ACS Spring Meeting 2021

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