Validation of cleaning procedures for highly potent drugs. I. Losoxantrone.
The validation of a procedure designed to clean glass and stainless steel surfaces after exposure to the experimental anticancer drug losoxantrone is described. The cleaning procedure, using water and hypochlorite bleach, was validated using a wipe test and a high-performance liquid chromatography (HPLC) method developed to quantitate low levels of losoxantrone. The HPLC method is shown to be linear and reproducible (relative standard deviation (RSD): 7.1% or less), with a detection limit of 2 ng/ml. Recoveries of 71.0%, 50.1%, and 57.6% were reproducibly obtained from the wipe pads, glass plates, and stainless steel plates, respectively, at levels of 70-140 ng per 100 cm2. The cleaning procedure is shown to clean glass and stainless steel plates to less than 20 ng and 17 ng losoxantrone per 100 cm2, respectively. These results demonstrate the need to fully characterize the recovery of drugs from surfaces and swabs in order to properly validate cleaning procedures.
Shea
J A
JA
DuPont Merck Pharmaceutical Company, Pharmaceutical R&D, Wilmington, Delaware 19880-0353, USA. sheaja@lldmpc.dnet.dupont.com
Shamrock
W F
WF
Abboud
C A
CA
Woodeshick
R W
RW
Nguyen
L Q
LQ
Rubino
J T
JT
Segretario
J
J
D000880:Anthraquinones / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004339:Drug Compounding / Q000295:instrumentation* / Q000379:methods; D005898:Glass; D011720:Pyrazoles / Q000737:chemistry*; D047069:Pyrazolones; D015203:Reproducibility of Results; D012973:Sodium Hypochlorite; D013193:Stainless Steel; D013499:Surface Properties; D014867:Water
D000880:Anthraquinones; D000970:Antineoplastic Agents; D011720:Pyrazoles; D047069:Pyrazolones; D014867:Water; D013193:Stainless Steel; C050637:losoxantrone; D012973:Sodium Hypochlorite