Liquid chromatographic method for simultaneous determination

Páginas: 13 (3100 palavras) Publicado: 16 de maio de 2011
Latin American Journal of Pharmacy
(formerly Acta Farmacéutica Bonaerense)
Lat. Am. J. Pharm. 28 (4): 525-30 (2009)
Original Article
Received: March 16, 2009
Accepted: April 6, 2009
Liquid Chromatographic Method for Simultaneous Determination
of Five Antineoplastic Drugs
Adélia M.P.P. ALCÂNTARA, Liliane M.A. VENUTO, Ana L.F. FRANÇA,
Elisabeth P. VIEIRA & Isarita MARTINS *
Laboratory ofToxicological Analysis, Department of Clinical and Toxicological Analysis,
University of Alfenas-MG/ Brazil- Av. Gabriel Monteiro da Silva, 714- Alfenas-MG- Brazil- 37130.000
SUMMARY. Therapeutic importance and benefices caused by antineoplastic drugs are unquestionable
however unfortunately well-known are their side effects. So, the extensive use and the exposure to multiple
agents may beat risk to health care workers involved in the preparation and administration of these
drugs. It is therefore important to have accurate methods for simultaneous analysis for evaluation of the
occupational exposure. In this study, we have developed a method for simultaneous determination of 5-fluorouracil
(5-FU), methotrexate (MTX), doxorubicin (DOX), cyclophosphamide (CP) and ifosfamide (IF).The assay was performed by HPLC-UV, detection in 195 nm, with a C18 column (250 x 4 mm, 5 μm) with
a similar guard- column. Mobile phase was constituted by water pH 4: acetonitrile: methanol (70:17:13,
v/v/v) with a flow of 0.4 mL min–1 up to 13 min and after this, 1 mL min–1. For cleaning of surfaces, we
used a solution of acetonitrile: methanol (50:50, v/v). The method presented a linearcalibration in a range
from 0.25 to 20 μg mL–1, for 5-FU and MTX and from 0.5 to 20 μg mL–1 for IF, DOX and CP, with correlation
coefficients (r2) upper to 0.997. The repeatability, expressed in terms of percent relative standard
deviation, was ≤ 10% and recovery was > 70%, in surfaces contaminated with the analytes. The results obtained
suggest that the method developed can be applicable forsimultaneous determination of the five
drugs studied and can be considered useful in exposure assessment.
Chemotherapy is the only systemic treatment
modality for cancer. However, cytotoxic drugs
are not selective for cancer cells, but also effect
the growth and reproduction of healthy cells 1.
It has been widely documented in the last 20
years that nurses and pharmacypersonnel
working in hospitals are exposed to antineoplastic
agents and the relevant exposure pathways
are through the skin and by inhalation 2.
During the preparation of cytotoxic infusions, a
variety of drug manipulations are performed, resulting
in the generation of aerosols and
droplets, which are known to contaminate the
areas in which they disperse into, including isolators
andsurrounding surfaces 3-11. Gloves utilized
by health care workers, in the chemotherapy
handling sites, can also increase the risk of
exposure in other areas of a hospital 12. Touzin
et al. 13 recently published a paper that evaluated
contamination on the external surfaces of cyclophosphamide
vials, during storage in pharmacy
departments, and demonstrated the drug
According to theInternational Agency for
Research on Cancer (IARC), at least nine alkylating
cytostatic drugs are classified as carcinogenic
to humans (Group 1). In addition, several
cytostatic drugs are classified, by the IARC, in
Groups 2A and 2B (probably and possibly carcinogenic
to humans, respectively) 14.
During the 1980’s, a series of guidelines and
recommendations from professional organizations
andgovernment agencies were developed
and promoted, recommending policies and procedures
for the safe handling of antineoplastic
agents 15.
A more recent report has been issued by Na526
tional Institute for Occupational Safety and
Health (NIOSH) 16 which released a comprehensive
analysis and description of specific...
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