New Rapid Stability indicating RP-UPLC Method for the Determination of Olaparib, its Related Substances and Degradation Products in Bulk drug and Dosage Form

MassChemSite for In-Depth Forced Degradation Analysis of PARP Inhibitors Olaparib, Rucaparib, and Niraparib

“…Generally, the ideal condition for carrying out stress tests is to promote degradation experiments of the drug in a purely aqueous stock solution. However, when the drug is poorly soluble in water, the use of co-solvent such as acetonitrile (ACN) is allowed to enhance the solubility. , In previous works, different ACN/H 2 O ratios have been employed for olaparib forced degradation studies. , Here, we decided to prepare a stock solution for olaparib in ACN/H 2 O (50:50; v/v %), as previously performed for other drugs (e.g., lansoprazole; cobicistat; alvimopan; and sumatriptan succinate). The degradation was then performed in a final solution of ACN/H 2 O (25:75; v/v %) after addition of the stress reagent dissolved in water.…”

“…Previous works have described the forced degradation of olaparib under basic, acidic, neutral, oxidative, dry heat, and photolytic stress conditions. − Sample preparation as well as the reaction conditions used to induce the drug’s forced degradation change slightly among the cited works. In addition, the DPs observed under the same conditions also differ among the reported studies.…”

“…Different results also emerge from the study of oxidative stress test, where some authors reported an effective degradation while others argue that the drug was stable. A general overview of the already reported studies on olaparib and its related stress impurities is summarized in Table S1 and Figure . − …”

“…A general overview of the already reported studies on olaparib and its related stress impurities is summarized in Table S1 and Figure 2 . 20 − 23 …”

“…Despite sharing the same mechanism of action, from the chemical structure point of view as well as their pharmacokinetic properties, these three drugs also have some substantial differences . At the time of our study, a few studies about the forced degradation of olaparib and rucaparib were published, − with tests limited to a single time point and in poorly comparable conditions, and sometimes leading to discordant results. In the case of niraparib, to the best of our knowledge, public data about its forced degradation are not publicly available.…”