Analysis of two commercially available bortezomib products: differences in assay of active agent and impurity profile.

The analytical properties of two commercially available bortezomib products (VELCADE(®) and Bortenat) were compared using nuclear magnetic resonance, mass spectrometry, high-performance liquid chromatography, and gas chromatography. The data showed differences between the two products. Based on these data, Bortenat samples contained more active ingredients than indicated by the label (mean, 116.5% and 117.9% of label, in 2-mg and 3.5-mg vials, respectively). In comparison, VELCADE samples contained a mean of 99.3% of active ingredient, which was consistent with the approved specification range (US, 90-110%; EU, 95-105%). Clinical data demonstrate that patients exposed to higher than recommended doses of bortezomib on the standard twice-weekly dosing schedule are likely to have an increased risk of major toxicities. Bortenat 2-mg vials contained an isovaleraldehyde impurity; the origin of this is unknown. Additionally, the ratio of boronic acid to boronic ester differed between Bortenat 2 mg (0.27:1) and 3.5 mg (0.13:1) and VELCADE (0.10:1) samples reconstituted in saline indicating that the Bortenat product is not equivalent to the VELCADE product.

Solid-state nuclear magnetic resonance spectroscopy--pharmaceutical applications.

Solid-state nuclear magnetic resonance (NMR) spectroscopy has become an integral technique in the field of pharmaceutical sciences. This review focuses on the use of solid-state NMR techniques for the characterization of pharmaceutical solids (drug substance and dosage form). These techniques include methods for (1) studying structure and conformation, (2) analyzing molecular motions (relaxation and exchange spectroscopy), (3) assigning resonances (spectral editing and two-dimensional correlation spectroscopy), and (4) measuring internuclear distances.