Research Article

AAPS PharmSciTech

, Volume 12, Issue 2, pp 461-467

First online:

Analysis of Two Commercially Available Bortezomib Products: Differences in Assay of Active Agent and Impurity Profile

  • Stephen R. ByrnAffiliated withDepartment of Industrial and Physical Pharmacy, Purdue University Email author 
  • , Patrick A. TishmackAffiliated withSSCI, A division of Aptuit
  • , Mark J. MiltonAffiliated withAnalytical Development, Millennium Pharmaceuticals, Inc.
  • , Helgi van de VeldeAffiliated withOrtho Biotech Oncology Research & Development, Janssen Pharmaceutica NV

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Abstract

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.

KEY WORDS

assay bortenat bortezomib impurities VELCADE