Development of Centrifugal Partition Chromatography for the Purification of Antibody-Drug Conjugates.

Monoclonal antibody-drug conjugates (ADCs) are an expanding therapeutic class of biomolecules for which relatively few analytical and preparative separation options exist. Purification of ADCs with a specific drug antibody ratio is even more challenging. We report the first application of countercurrent separation (CCS) to this problem.

Pharmaceutical analysis by NMR can accommodate strict impurity thresholds: The case of choline.

The ICH guidelines recommend reporting thresholds for regular impurities in drug substances at the level of 0.05% or 0.03% (w/w) depending on the maximum daily intake.

Rufomycins or Ilamycins: Naming Clarifications and Definitive Structural Assignments.

Rufomycin and ilamycin are synonymous for the same class of cyclopeptides, currently encompassing 33 structurally characterized isolates and 9 semisynthetic derivatives. Elucidation of new structures prioritized the consolidation of the names and established the structures of four diastereoisomeric rufomycins with a 2-piperidinone, named rufomycins 4-7, including full H/C NMR assignments. The characteristic HSQC cross-peak for the CH-5, the hemiaminal carbon in amino acid #5, allows assignment of the stereocenters C-4 and C-5 within this ring.

Plain H nuclear magnetic resonance analysis streamlines the quality control of antiviral favipiravir and congeneric World Health Organization essential medicines.

Favipiravir is an established antiviral that is currently being assessed as an investigational drug for the treatment of COVID-19. Favipiravir is strikingly similar to two molecules that the World Health Organization (WHO) lists as essential medicines, which also consist of a six-membered aromatic N-heterocycle bearing a carboxamide function: the anti-tuberculosis agent, pyrazinamide, and nicotinamide, also known as vitamin B . We demonstrate the utility of H nuclear magnetic resonance (NMR) profiling, an emerging pharmacopoeial tool, for the highly specific identification, selective differentiation of congeners, and subsequent detection of drug falsification or adulteration of these medicines.

Quantum mechanical NMR full spin analysis in pharmaceutical identity testing and quality control.

Issues related to pharmaceutical quality are arising at an alarming rate. Pharmaceutical quality concerns both the Active Pharmaceutical Ingredients (APIs) and the Finished Drug Product/ Formulation. Recently, there has been a significant increase in the number of reports of harmful impurities in marketed drug formulations.

Synthesis and antimicrobial evaluation of piperic acid amides and their lower homologues.

Seven piperic acid amides along with their lower homologs (12) were synthesized using HATU-DIPEA coupling reagent. All the synthesized derivatives were evaluated for their antibacterial activities against Staphylococcus aureus, Pseudomonas aeruginosa, and vancomycin-resistant P. aeruginosa.

Separation of Unprecedented Degradants of Domperidone by Ultra-Performance Convergence Chromatography and Their Structure Elucidation.

Domperidone, a gastroprokinetic agent, is a common drug to treat emesis. It was subjected to acid, base-mediated hydrolysis, peroxide-mediated oxidation, photolysis and thermal degradation according to ICH guidelines to observe stability of the selected drug under the stress conditions. Although the drug is resistant to base hydrolysis, photolysis and thermal stressors, two degradants (DP-ISO1 and DP-ISO2) were formed in acid mediated hydrolysis.

Structure elucidation of novel degradation products of thiocolchicoside by NMR spectroscopy.

Thiocolchicoside is a natural product analogue often used for its spasmolytic action. To know more about its stability under various stress conditions, the drug was stirred in acid, base and peroxide solutions. In acid hydrolysis, two products were obtained and in both, the glucose got cleaved.

Flavone C-glycosides from Trichuriella monsoniae (L.f.) Bennet.

In the first phytochemical investigation of Trichuriella monsoniae, three known flavonoidal C-glycosides, isoswertisin 1, 2″-O-β-d-galactosyl isoswertisin 2 and 2″-O-β-d-xylosyl isoswertisin 3 were isolated from the methanolic extract of the whole plant. Their structures were elucidated by extensive NMR spectroscopic studies including 2D NMR and HRMS, and the structure of 2 was supported by single crystal X-ray data studies. Further, NMR assignments for 3 are being reported for the first time.

New malabaricane triterpenes from the oleoresin of Ailanthus malabarica.

Ten malabaricane type triterpenes were isolated from the oleoresin of Ailanthus malabarica, out of which six (1-6) were new. For three of the known compounds (7-9), NMR assignments are being reported for the first time. Compound 10, a known one, is a new report from this source.