Isolation, Identification, and Characterization of an Unknown Impurity in Lovastatin EP

Belwal, Chandrakant; Goyal, Praveen Kumar; Balte, Anup; Kolhe, Sandeep; Chauhan, Kamlesh R.; Rawat, Ajay Singh; Vardhan, Anand

doi:10.3797/scipharm.1305-04

Cited by 12 publications

(3 citation statements)

References 4 publications

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“…% of impurities indicated by the manufacturer, which could include the S-H-containing malonyl-CoA molecule [37]. The acid form of lovastatin is also known to sometimes be present as an impurity [65], but we see no evidence for the presence of carboxylic acid monomers or dimers in our measured spectra. There could also be a contribution to the C=C symmetric stretch region of the spectrum from C=N vibrations of in malonyl-CoA impurities.…”

Section: Ir Spectroscopymentioning

confidence: 53%

Bulk and Surface Conformations in Solid-State Lovastatin: Spectroscopic and Molecular Dynamics Studies

et al. 2021

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Conformational flexibility in molecules can give rise to a range of functional group terminations at crystal surfaces and dynamic disorder in the bulk. In this work, we explore the conformational behavior of the drug molecule lovastatin in the crystallographically disordered solid and at crystal surfaces through a combination of computational modeling and spectroscopy. Gas-phase and periodic quantum-chemical calculations are used to study the potential energy surface associated with rotatable bonds to examine the disorder in bulk. These calculations are combined with vibrational and X-ray photoelectron spectroscopy measurements to obtain insight into the conformations in bulk and at the surface. Our MD simulations show that the bulk disorder is driven by cooperative motion of the butyl group on the S-butanoate moiety along one crystallographic direction beyond a unit cell. The calculations show that the O-H group can rotate relatively freely between two low-energy conformers in the gas phase but is locked in position by intermolecular H-bonding interactions in the bulk crystal, and we find tentative spectroscopic evidence for the second conformer being present at the surface. We also comment on the relative utility of these different techniques for studying molecular conformation in bulk and at surfaces and highlight possible areas for future developments.

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Section: Ir Spectroscopymentioning

confidence: 53%

Bulk and Surface Conformations in Solid-State Lovastatin: Spectroscopic and Molecular Dynamics Studies

et al. 2021

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“…[1] was separated by preparative HPLC followed by structure elucidation by MS and NMR. The structure found characterizes a by-product of the biosynthesis of lovastatin by fermentation [23].…”

Section: Identification Of Impurities In Drugsmentioning

confidence: 99%

Identification in drug quality control and drug research

Gǒrög

2015

TrAC Trends in Analytical Chemistry

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“…An important factor for the safety and effectiveness of pharmaceuticals is the purity of the drug, making impurity profiling critical [7,8]. Various unknown impurities could form in the drug product during formulation, manufacturing, and storage as well as in the synthesis of the active pharmaceutical ingredient (API) [9].…”

Section: Introductionmentioning

confidence: 99%

Detection and Identification of an Unknown Impurity in Ephedrine HCl 5 mg/mL Cyclic Olefin Syringes: Formulation Development

et al. 2023

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An unknown impurity was detected in in-house prepared ephedrine hydrochloride (HCl) 5 mg/mL prefilled sterilized syringes when applying a stability-indicating British Pharmacopoeia 2018 impurity method for ephedrine injection. Ultraviolet, chromatographic, mass spectral, and physicochemical methods were combined to identify the unknown impurity. The unknown impurity was identified as methcathinone, which is generated from ephedrine drug substance through an oxidation reaction. A formulation study, in which different process adjustments were tested, was carried out to reduce the amount of unknown impurity. Nitrogen gassing in combination with 0.05 M citrate buffer addition proved to be the most potent process adjustment in reducing methcathinone formation in ephedrine HCl 5 mg/mL prefilled sterilized syringes after 4 months of storage in the dark at room temperature (20 °C ± 5 °C). More detailed research on the long-term stability of the reformulated ephedrine HCl drug product is currently underway, with promising results for up to 9 months gathered already.

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Isolation, Identification, and Characterization of an Unknown Impurity in Lovastatin EP

Cited by 12 publications

References 4 publications

Bulk and Surface Conformations in Solid-State Lovastatin: Spectroscopic and Molecular Dynamics Studies

Bulk and Surface Conformations in Solid-State Lovastatin: Spectroscopic and Molecular Dynamics Studies

Identification in drug quality control and drug research

Detection and Identification of an Unknown Impurity in Ephedrine HCl 5 mg/mL Cyclic Olefin Syringes: Formulation Development

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