Impact of Manufacturing Process and Compounding on Properties and Quality of Follow-On GLP-1 Polypeptide Drugs.

Purpose: The prevalence of follow-on and compounded products of glucagon-like peptide-1 analogs is increasing. We assessed glucagon-like peptide-1 analogs semaglutide and liraglutide for purity, potential immunogenicity, and expected stability, by comparing a representative selection of commercially available follow-on drug substances (DSs) and drug products (DPs) with their corresponding originators.

Methods: Tests included several chromatography methods coupled with ultraviolet and mass spectrometry detectors, inductively coupled plasma optical emission spectroscopy, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, dissolution analyses, in silico peptide/major histocompatibility complex II-binding prediction, and fibrillation assays.

Production of unusual dispiro metabolites in Pestalotiopsis virgatula endophyte cultures: HPLC-SPE-NMR, electronic circular dichroism, and time-dependent density-functional computation study.

The endophytic fungus Pestalotiopsis virgatula, derived from the plant Terminalia chebula and previously found to produce a large excess of a single metabolite when grown in the minimal M1D medium, was induced to produce a variety of unusual metabolites by growing in potato dextrose broth medium. Analysis of the fermentation medium extract was performed using an HPLC-PDA-MS-SPE-NMR hyphenated system, which led to the identification of a total of eight metabolites (1-8), six of which are new. Most of the metabolites are structurally related and are derivatives of benzo[c]oxepin, rare among natural products.

Antifungal metabolites from fungal endophytes of Pinus strobus.

The extracts of five foliar fungal endophytes isolated from Pinus strobus (eastern white pine) that showed antifungal activity in disc diffusion assays were selected for further study. From these strains, the aliphatic polyketide compound 1 and three related sesquiterpenes 2-4 were isolated and characterized. Compound 2 is reported for the first time as a natural product and the E/Z conformational isomers 3 and 4 were hitherto unknown.

Identification of adulterants in a Chinese herbal medicine by LC-HRMS and LC-MS-SPE/NMR and comparative in vivo study with standards in a hypertensive rat model.

Based on anecdotal evidence of anti-hypertensive effect of Gold Nine Soft Capsules, an in vivo study of this complex Chinese "herbal-based" medicine was initiated. Dosage of the content of Gold Nine capsules in spontaneous hypertensive rats showed a remarkably good effect. This led to further investigation of the components of the preparation and eventual identification of three known anti-hypertensive drugs; amlodipine, indapamide and valsartan, which were not declared on the label.

HPLC-SPE-NMR identification of a novel metabolite containing the benzo[c]oxepin skeleton from the endophytic fungus Pestalotiopsis virgatula culture.

HPLC-SPE-NMR analysis of a crude extract of fermentation broth of cultured PESTALOTIOPSIS VIRGATULA isolate TC-320 from TERMINALIA CHEBULA Retz. (Combretaceae) disclosed the presence of a simple but unprecedented low-molecular-weight metabolite, 9-hydroxybenzo[ C]oxepin-3[1 H]-one, subsequently isolated by a targeted purification procedure.

Accelerated dereplication of crude extracts using HPLC-PDA-MS-SPE-NMR: quinolinone alkaloids of Haplophyllum acutifolium.

Direct hyphenation of analytical-scale high-performance liquid chromatography, photo-diode array detection, mass spectrometry, solid-phase extraction and nuclear magnetic resonance spectroscopy (HPLC-PDA-MS-SPE-NMR) has been used for accelerated dereplication of crude extract of Haplophyllum acutifolium (syn. Haplophyllum perforatum). This technique allowed fast on-line identification of six quinolinone alkaloids, named haplacutine A-F, as well as of acutine, haplamine, eudesmine, and 2-nonylquinolin-4(1H)-one.

Piperidine and tetrahydropyridine alkaloids from Lobelia siphilitica and Hippobroma longiflora.

The hyphenated technique HPLC-PDA-MS-SPE-NMR was used to assist targeted preparative-scale isolation of constituents of Lobelia siphilitica and Hippobroma longiflora (both Campanulaceae). This resulted in the isolation of two new alkaloids, (S)-2-[(2S,6R)-1-methyl-6-(2-oxo-2-phenylethyl)piperidin-2-yl]-1-phenylethyl acetate (3) and 6-[(E)-2-(3-methoxyphenyl)ethenyl]-2,3,4,5-tetrahydropyridine (4), the latter possessing a skeleton hitherto unseen among alkaloids of Lobelia and related genera. Lobeline (1), (1S,1'S)-2,2'-[(2R,6S)-1-methylpiperidine-2,6-diyl]bis(1-phenylethanol) (2), and lobetyolin (5) were also isolated.