title: Comparison of three generic vancomycin products using liquid chromatography-mass spectrometry and an online tool.
abstract: OBJECTIVE
  Three different generic vancomycin products were compared using liquid chromatography-mass spectrometry (LC-MS) and open-access metabolomic tools.
  
  
  METHODS
  Single-lot samples of vancomycin hydrochloride from three different manufacturers (Hospira, APP Pharmaceuticals, and Pfizer) were reconstituted and injected into a high-resolution LC-MS system. The mass spectral fingerprints were compared for similarity of nonvancomycin B components using the XCMS Online system through Scripps University. Significance was defined as a p of ≤0.01 and a fold change of ≥1.5. The concentration of vancomycin B in each product was also measured using LC-MS on days 0, 1, 2, 4, 7, 10, and 14.
  
  
  RESULTS
  Qualitative comparisons of the products using the XCMS Online interface indicated the presence of significant differences among the products at the time of reconstitution; however, these variations seemed to converge after 14 days of storage. The concentration profiles of vancomycin B during refrigerated storage did not differ significantly among the three products. XCMS Online analyses revealed that the Pfizer and Hospira products were the most similar to each other.
  
  
  CONCLUSIONS
  While there were no significant differences found in the concentration of vancomycin B among Pfizer, APP, and Hospira products, there were differences in their initial mass spectral analysis after reconstitution. Liquid chromatography-tandem mass spectrometry profiles of the ions or isotopes present in the three products showed significant differences in impurities such as crystalline degradation product (CDP)-1 and CDP intermediate. After 14 days of refrigerated storage, the differences among the products converged, and fewer distinct features could be detected.
authors.affiliation: Paul O. Lewis, Pharm.D., BCPS, is Clinical Pharmacy Specialist-Infectious Diseases, Johnson City Medical Center, Johnson City, TN. Loren M. Kirk, B.S., is Pharm.D. Candidate; and Stacy D. Brown, Ph.D., is Associate Professor of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City. lewispo@msha.com.
authors.forename: Paul O
authors.initials: PO
authors.lastname: Lewis
authors.affiliation: Paul O. Lewis, Pharm.D., BCPS, is Clinical Pharmacy Specialist-Infectious Diseases, Johnson City Medical Center, Johnson City, TN. Loren M. Kirk, B.S., is Pharm.D. Candidate; and Stacy D. Brown, Ph.D., is Associate Professor of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City.
authors.forename: Loren M
authors.initials: LM
authors.lastname: Kirk
authors.affiliation: Paul O. Lewis, Pharm.D., BCPS, is Clinical Pharmacy Specialist-Infectious Diseases, Johnson City Medical Center, Johnson City, TN. Loren M. Kirk, B.S., is Pharm.D. Candidate; and Stacy D. Brown, Ph.D., is Associate Professor of Pharmaceutical Sciences, Bill Gatton College of Pharmacy, East Tennessee State University, Johnson City.
authors.forename: Stacy D
authors.initials: SD
authors.lastname: Brown
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D004356:Drug Storage; D016568:Drugs, Generic / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D009862:Online Systems; D012034:Refrigeration; D013997:Time Factors; D014640:Vancomycin / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D016568:Drugs, Generic; D014640:Vancomycin