Studies on repository compound stability in DMSO under various conditions.
The chemical stability of repository compounds is affected by various environmental conditions during long-term storage. Studies were carried out to evaluate the effects of the following potential causes of instability of compounds in DMSO at a 10-mM concentration: water, oxygen, freeze/thaw cycles, and storage container material. A set of compounds was selected for the study based on structural diversity and functional group representation. Compound concentration was determined with liquid chromatography/ultraviolet spectroscopy/mass spectrometry (LC/UV/MS) analysis relative to an internal standard added to each sample. An accelerated study was conducted, and results demonstrate that most compounds are stable for 15 weeks at 40 degrees C. Water is more important in causing compound loss than oxygen. The freeze/thaw cycle study was done with freezing at -15 degrees C and thawing under nitrogen atmosphere at 25 degrees C. Two methods were used to redissolve compounds after thawing: agitation and repeated aspiration/dispense. The results indicate no significant compound loss after 11 freeze/thaw cycles. Compound recovery was also measured from glass and polypropylene containers for 5 months at room temperature, and no significant difference was found for these 2 types of containers.
Cheng
Xueheng
X
Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA. xueheng.cheng@abbott.com
Hochlowski
Jill
J
Tang
Hua
H
Hepp
Darlene
D
Beckner
Carl
C
Kantor
Stan
S
Schmitt
Robert
R
D002853:Chromatography, Liquid / Q000379:methods*; D003451:Cryoprotective Agents / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004355:Drug Stability; D004356:Drug Storage; D005615:Freezing; D005898:Glass / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D008956:Models, Chemical; D010100:Oxygen / Q000737:chemistry; D011126:Polypropylenes / Q000737:chemistry; D012997:Solvents / Q000494:pharmacology; D013048:Specimen Handling; D013696:Temperature; D013997:Time Factors; D014466:Ultraviolet Rays; D014867:Water / Q000737:chemistry
D003451:Cryoprotective Agents; D011126:Polypropylenes; D012997:Solvents; D014867:Water; D010100:Oxygen; D004121:Dimethyl Sulfoxide