# Structure Identification and Risk Assurance of Unknown Impurities in Pramipexole Oral Drug Formulation

## TL;DR

This paper identifies and analyzes unknown impurities in a Parkinson's drug, Pramipexole, and assesses their potential risk to drug safety and effectiveness.

## Contribution

The study identifies two unknown impurities in Pramipexole formulations and evaluates their binding affinity risks using molecular simulations.

## Key findings

- Two unknown impurities were identified in Pramipexole dihydrochloride using UPLC-HRMS.
- The presence of mannitol in the formulation enriched these impurities.
- Molecular docking showed pramipexole has higher receptor binding affinity than its impurity adducts.

## Abstract

Impurities compounds in any pharmaceutical product or drug substance are inevitable from a chemistry point of view. The quality and safety of a pharmaceutical product are also significantly affected by these impurities content; therefore, impurities need to be identified and characterized through the use of appropriate analytical methods. Pramipexole is a nonergot dopamine agonist used to treat various Parkinson's disease symptoms. Two unknown impurities were detected from a pramipexole dihydrochloride solid dosage form. These impurities were identified and characterized using ultra-performance liquid chromatography coupled with high-resolution mass spectroscopy (UPLC-HRMS). These impurities were found to be enriched when mannitol existed in the formulation. The structure and mechanism involved in the existence of the impurities were proposed. Furthermore, observation of the binding affinity potential risk of these impurities to the pramipexole receptor has also been demonstrated through molecular docking and molecular dynamics simulation study. The binding energy result showed that pramipexole interaction with dopamine receptors D2 and D3 was higher than pramipexole mannose adduct and pramipexole ribose adduct.