A UHPLC-UV-QTOF study on the stability of carfilzomib, a novel proteasome inhibitor.

This study addresses the lack of data on the stability of carfilzomib, a newly approved proteasome-inhibiting anticancer drug. A new stability-indicating UHPLC-UV method for analysis of carfilzomib was developed and validated within the concentrations of 10-250 µg/mL. The aforementioned method was utilized to evaluate the effects of forced degradation and to investigate the degradation kinetics, as well as to examine drug stability in a pharmaceutical formulation. A UHPLC-QTOF method was utilized to identify the principal degradation products. It was found that carfilzomib: (1) is stable at neutral and slightly acidic pH, but prone to degradation at both high and low pH; (2) is acceptably stable in the pharmaceutical formulation; but (3) is prone to oxidation and photodegradation. Carfilzomib degradation followed first-order kinetics. The decomposition products resulted from peptide bond hydrolysis, epoxide hydrolysis, hydrogen chloride addition, base-catalyzed Robinson-Gabriel reaction, tertiary amine oxidation and isomerization. Our results document, for the first time, the inherent stability of carfilzomib and provide information about the identity of its degradation products. These results highlight the stability issues that need to be kept in mind for handling and storage of carfilzomib.

Quantitative determination of phenolic compounds by UHPLC-UV-MS and use of partial least-square discriminant analysis to differentiate chemo-types of Chamomile/Chrysanthemum flower heads.

A new rapid UHPLC-UV-QTOF/MS method has been developed for the simultaneous analysis of nine phenolic compounds [(Z)-2-ß-d-glucopyranosyloxy-4-methoxycinnamic acid (cis-GMCA), chlorogenic acid, (E)-2-ß-d-glucopyranosyloxy-4-methoxycinnamic acid (trans-GMCA), quercetagetin-7-O-ß-d-glucopyranoside, luteolin-7-O-ß-d-glucoside, apigenin-7-O-ß-d-glucoside, chamaemeloside, apigenin 7-O-(6″-O-acetyl-ß-d-glucopyranoside), apigenin] and one polyacetylene (tonghaosu) from the flower heads of Chamomile/Chrysanthemum samples. The chromatographic separation was achieved using a reversed phase C18 column with a mobile phase of water and acetonitrile, both containing 0.05% formic acid. The ten compounds were completely separated within 15min at a flow rate of 0.25mL/min with a 2µL injection volume. The different chemo-types of Chamomiles/Chrysanthemum displayed variations in the presence of chemical constituents. German Chamomile samples confirmed the presence of cis-GMCA, trans-GMCA, apigenin-7-O-ß-d-glucoside and tonghaosu as major constituents whereas Roman chamomile samples confirmed the presence of chamamaeloside and apigenin as major compounds. The Chrysanthemum morifolium samples showed the presence of luteolin-7-O-ß-d-glucose as the major compound. The method was applied for the analysis of various commercial products including capsules, tea bags, body and hair care products. LC-mass spectrometry with electrospray ionization (ESI) interface method is described for the evaluation of ten compounds in plant samples and commercial products. This method involved the detection of [M+Na](+) and [M+H](+) ions in the positive mode. Partial least squares discriminant analysis (PLS-DA) was used to visualize commercial samples quality and may be of value for discriminating between chamomile types and Chrysanthemum with regards to the relative content of individual constituents. The results indicated that the method is suitable as a quality control test for various Chamomile/Chrysanthemum samples and market products.