The extent of amotosalen photodegradation during photochemical treatment of platelet components correlates with the level of pathogen inactivation.
BACKGROUND
Amotosalen plus ultraviolet A (UVA) light inactivates a broad range of bacteria, viruses, protozoa, and leukocytes in platelet (PLT) and plasma components. Upon UVA illumination a small fraction of amotosalen reacts with the nucleic acid of contaminating pathogens and residual white blood cells and the remaining fraction undergoes photodegradation into defined photoproducts. The levels of amotosalen and photoproducts can be accurately quantified.


METHODS
This study evaluated the relationship between the extent of photodegradation of amotosalen and the level of pathogen inactivation in PLT components. PLT components containing of 3.78×10(11) to 7.23×10(11) PLTs in 300 to 450 mL of 35% to 50% plasma and 50% to 65% PLT additive solution and up to 5×10(6) red blood cells (RBCs)/mL were prepared. Each component was contaminated with 10(5) to 10(6) colony-forming units/mL Klebsiella pneumoniae and treated with 115 to 200 µmol/L amotosalen and 0 to 3 J/cm2 UVA light. For each treatment condition, the level of K. pneumoniae inactivation (log-reduction) was measured by microbiologic methods. The initial and postillumination amotosalen concentrations (µmol/L) were determined by high-performance liquid chromatography.


RESULTS
For a defined set of treatment conditions, the extent of amotosalen photodegradation was consistent and reproducible. The bacterial log-reduction correlated linearly with the extent of amotosalen photodegradation with a regression correlation coefficient (r2) between 0.845 and 0.890 regardless of the treatment variables such as PLT content, component volume, plasma content, RBC content, initial amotosalen concentration, and UVA dose.


CONCLUSIONS
This study demonstrated that the extent of amotosalen photodegradation can serve as an intrinsic actinometer which directly correlated with the level of pathogen inactivation.
Liu
Weiqun
W
Cerus Corp., Concord, California 94520, USA. wliu@cerus.com
Cimino
George D
GD
Corash
Laurence
L
Lin
Lily
L
D001792:Blood Platelets / Q000187:drug effects* / Q000382:microbiology* / Q000528:radiation effects; D004912:Erythrocytes / Q000166:cytology; D011564:Furocoumarins / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000528:radiation effects; D010782:Photolysis; D013234:Stem Cells / Q000187:drug effects / Q000528:radiation effects; D014466:Ultraviolet Rays
D011564:Furocoumarins; C118577:amotosalen