Analytical and biological inequivalence of two commercial formulations of the antitumor agent bleomycin

Robert T Dorr, Ross Meyers, Kristi Snead, James D. Liddil

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at least 55-75% bleomycin A2 and 25-32% bleomycin B2 fractional composition. Two bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb Oncology, Princeton, N.J.) and bleomycin HCl (Tianjin Hebei Pharmaceutical, Tianjin, China) were compared analytically and biologically. Reverse-phase high-performance liquid chromatography (HPLC) analyses using the USP methodology showed that Blenoxane contained primarily (69%) bleomycin A2 and 29.3% bleomycin B2. In contrast, Tianjin-supplied bleomycin HCl contained 97% bleomycin A5 fraction. In vitro tumor cell growth inhibition assays showed equivalent activity in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L-1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16 melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor growth inhibition at the expense of greater drug-induced lethality at higher dose levels. These studies show there are significant differences in two international bleomycin formulations. These compositional differences lead to altered biologic effects.

Original languageEnglish (US)
Pages (from-to)149-154
Number of pages6
JournalCancer Chemotherapy and Pharmacology
Volume42
Issue number2
DOIs
StatePublished - 1998

Fingerprint

Bleomycin
Antineoplastic Agents
Tumors
Bearings (structural)
Leukemia L1210
Neoplasms
Oncology
Glycopeptides
High performance liquid chromatography
Cell growth
Reverse-Phase Chromatography
Growth
Human Activities
Pharmaceutical Preparations
Ovarian Neoplasms
Melanoma
Assays
China
High Pressure Liquid Chromatography
Cells

Keywords

  • Anticancer
  • Bleomycin
  • Equivalence

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Analytical and biological inequivalence of two commercial formulations of the antitumor agent bleomycin. / Dorr, Robert T; Meyers, Ross; Snead, Kristi; Liddil, James D.

In: Cancer Chemotherapy and Pharmacology, Vol. 42, No. 2, 1998, p. 149-154.

Research output: Contribution to journalArticle

@article{99a3a7260f8e4e079b6d2c888019ac0e,
title = "Analytical and biological inequivalence of two commercial formulations of the antitumor agent bleomycin",
abstract = "Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at least 55-75{\%} bleomycin A2 and 25-32{\%} bleomycin B2 fractional composition. Two bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb Oncology, Princeton, N.J.) and bleomycin HCl (Tianjin Hebei Pharmaceutical, Tianjin, China) were compared analytically and biologically. Reverse-phase high-performance liquid chromatography (HPLC) analyses using the USP methodology showed that Blenoxane contained primarily (69{\%}) bleomycin A2 and 29.3{\%} bleomycin B2. In contrast, Tianjin-supplied bleomycin HCl contained 97{\%} bleomycin A5 fraction. In vitro tumor cell growth inhibition assays showed equivalent activity in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L-1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16 melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor growth inhibition at the expense of greater drug-induced lethality at higher dose levels. These studies show there are significant differences in two international bleomycin formulations. These compositional differences lead to altered biologic effects.",
keywords = "Anticancer, Bleomycin, Equivalence",
author = "Dorr, {Robert T} and Ross Meyers and Kristi Snead and Liddil, {James D.}",
year = "1998",
doi = "10.1007/s002800050798",
language = "English (US)",
volume = "42",
pages = "149--154",
journal = "Cancer Chemotherapy and Pharmacology",
issn = "0344-5704",
publisher = "Springer Verlag",
number = "2",

}

TY - JOUR

T1 - Analytical and biological inequivalence of two commercial formulations of the antitumor agent bleomycin

AU - Dorr, Robert T

AU - Meyers, Ross

AU - Snead, Kristi

AU - Liddil, James D.

PY - 1998

Y1 - 1998

N2 - Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at least 55-75% bleomycin A2 and 25-32% bleomycin B2 fractional composition. Two bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb Oncology, Princeton, N.J.) and bleomycin HCl (Tianjin Hebei Pharmaceutical, Tianjin, China) were compared analytically and biologically. Reverse-phase high-performance liquid chromatography (HPLC) analyses using the USP methodology showed that Blenoxane contained primarily (69%) bleomycin A2 and 29.3% bleomycin B2. In contrast, Tianjin-supplied bleomycin HCl contained 97% bleomycin A5 fraction. In vitro tumor cell growth inhibition assays showed equivalent activity in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L-1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16 melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor growth inhibition at the expense of greater drug-induced lethality at higher dose levels. These studies show there are significant differences in two international bleomycin formulations. These compositional differences lead to altered biologic effects.

AB - Bleomycin is an antitumor agent which is a mixture of glycopeptides containing at least 55-75% bleomycin A2 and 25-32% bleomycin B2 fractional composition. Two bleomycin formulations, bleomycin sulfate, USP (Blenoxane, Bristol-Myers Squibb Oncology, Princeton, N.J.) and bleomycin HCl (Tianjin Hebei Pharmaceutical, Tianjin, China) were compared analytically and biologically. Reverse-phase high-performance liquid chromatography (HPLC) analyses using the USP methodology showed that Blenoxane contained primarily (69%) bleomycin A2 and 29.3% bleomycin B2. In contrast, Tianjin-supplied bleomycin HCl contained 97% bleomycin A5 fraction. In vitro tumor cell growth inhibition assays showed equivalent activity in human OVCAR-3 ovarian cancer cells and slightly greater potency in murine L-1210 leukemia cells for the Tianjin formulation. In C57/B1 mice bearing B-16 melanoma tumors, Tianjin-supplied bleomycin produced slightly greater tumor growth inhibition at the expense of greater drug-induced lethality at higher dose levels. These studies show there are significant differences in two international bleomycin formulations. These compositional differences lead to altered biologic effects.

KW - Anticancer

KW - Bleomycin

KW - Equivalence

UR - http://www.scopus.com/inward/record.url?scp=0031833540&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031833540&partnerID=8YFLogxK

U2 - 10.1007/s002800050798

DO - 10.1007/s002800050798

M3 - Article

C2 - 9654115

AN - SCOPUS:0031833540

VL - 42

SP - 149

EP - 154

JO - Cancer Chemotherapy and Pharmacology

JF - Cancer Chemotherapy and Pharmacology

SN - 0344-5704

IS - 2

ER -