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Citation
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HERO ID
4116485
Reference Type
Journal Article
Title
Stability of cyclophosphamide in extemporaneous oral suspensions
Author(s)
Kennedy, R; Groepper, D; Tagen, M; Christensen, R; Navid, F; Gajjar, A; Stewart, CF
Year
2010
Is Peer Reviewed?
Yes
Journal
Annals of Pharmacotherapy
ISSN:
1060-0280
EISSN:
1542-6270
Volume
44
Issue
2
Page Numbers
295-301
Language
English
PMID
20103616
DOI
10.1345/aph.1M578
Web of Science Id
WOS:000274617100006
Abstract
BACKGROUND:
Cyclophosphamide, an alkylating agent, is widely used for the treatment of many adult and pediatric malignancies. The stability of cyclophosphamide in aqueous- and methylcellulose-based oral suspending vehicles is currently unknown.
OBJECTIVE:
To develop and validate a stability-indicating high-performance liquid chromatography (HPLC) method to measure cyclophosphamide concentrations in simple syrup and Ora-Plus, and assess the 56-day chemical stability and physical appearance of cyclophosphamide in these suspensions at both room temperature (22 degrees C) and 4 degrees C.
METHODS:
The intravenous formulation of cyclophosphamide was diluted to 20 mg/mL in NaCl 0.9%, compounded 1:1 with either suspending vehicle, and stored in the dark in 3-mL amber polypropylene oral syringes at 4 degrees C and 22 degrees C. Aliquots from each syringe were obtained on days 0, 3, 7, 14, 21, 28, 35, 42, 49, and 56 and assayed using the validated stability-indicating HPLC-UV method. A C18 analytical column was used to separate cyclophosphamide from the internal standard, ifosfamide, with a mobile phase of 21% acetonitrile in 79% sodium phosphate buffer. The suspension was examined for odor change, visually examined under normal fluorescent light for color change, and examined under a light microscope for evidence of microbial growth.
RESULTS:
Samples of cyclophosphamide in both simple syrup and Ora-Plus were stable when kept at 4 degrees C for at least 56 days. At room temperature, cyclophosphamide in simple syrup and Ora-Plus had a shelf life of 8 and 3 days, respectively. No changes in color or odor or evidence of microbial growth were observed.
CONCLUSIONS:
Cyclophosphamide can be extemporaneously prepared in simple syrup or Ora-Plus and stored for at least 2 months under refrigeration without significant degradation.
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