Stability of cyclophosphamide in extemporaneous oral suspensions.
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.
Kennedy
Rachel
R
Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
Groepper
Daniel
D
Tagen
Michael
M
Christensen
Robbin
R
Navid
Fariba
F
Gajjar
Amar
A
Stewart
Clinton F
CF
D018906:Antineoplastic Agents, Alkylating / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003520:Cyclophosphamide / Q000737:chemistry*; D004355:Drug Stability; D004356:Drug Storage; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D012034:Refrigeration; D013535:Suspensions; D013696:Temperature
D018906:Antineoplastic Agents, Alkylating; D014677:Pharmaceutical Vehicles; D013535:Suspensions; D003520:Cyclophosphamide