Synthesis of Impurities of Pramipexole Dihydrochloride

Hu, Tianwen; Yang, Feipu; Jiang, Tao; Chen, Weiming; Zhang, Jian; Li, Jian Feng; Jiang, Xiangrui; Shen, Jingshan

doi:10.1021/acs.oprd.6b00182

Cited by 5 publications

(2 citation statements)

References 18 publications

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“…It is well-established as a treatment option for motor symptoms at all stages of Parkinson's disease (PD). Also, this drug is efective in the treatment of idiopathic and secondary restless legs syndrome (RLS) and in treatment-resistant patients as well [1][2][3][4].…”

Section: Introductionmentioning

confidence: 99%

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

Tjandrawinata,

Cahyana,

Nugroho

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

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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.

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Section: Introductionmentioning

confidence: 99%

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

Tjandrawinata,

Cahyana,

Nugroho

et al. 2024

Advances in Pharmacological and Pharmaceutical Sciences

View full text Add to dashboard Cite

show abstract

“…Pramipexole [( S )-2-amino-4,5,6,7-tetra-hydro-6-(propylamino) benzothiazole, molecular formula C 10 H 17 N 3 S; relative molecular mass 211.33] is a white to off-white crystalline powder with suitable Log P o/w value of 2.3 and solubility of 10.92 mg/L in water at 305.15 K, which is marketed in the USA in 2005 under the brand name MIRAPEX and developed as a second-generation non-ergot dopamine receptor agonist by Boehringer Ingelheim. , It has been recognized as a treatment option for motor symptoms at all stages of Parkinson’s disease. − According to the published literature, the synthetic routes of pramipexole mainly include the following: (1) with 2,6-diamino-4,5,6,7-tetrahydro benzothiazole as the starting material, propionic anhydride was added to anhydrous tetrahydrofuran for reaction to prepare ( S )-2-amino-6-propionamido-4,5,6,7-tetrahydro benzothiazole, and then pramipexole base was obtained by a reduction reaction in borane tetrahydrofuran solution; (2) the same starting material reacted with n -propionaldehyde in DMF to generate Schiff base, and then sodium borohydride or derivatives were added for reduction to obtain pramipexole . However, because of the tendency of both amino groups to form Schiff bases, there may be byproducts in the synthesis process route.…”

Section: Introductionmentioning

confidence: 99%