Reduction of non-specific adsorption of drugs to plastic containers used in bioassays or analyses.
BACKGROUND
Non-specific adsorption (NSA) of drugs to plastic or glass containers used in clinical use is well known, but methods for reducing NSA have been rarely reported. We assessed the NSA to various containers and then investigated methods to reduce NSA.


METHODS
Probe drugs (methotrexate, warfarin, chloroquine, propranolol, verapamil, digoxin and paclitaxel) dissolved in water were incubated in conventional or low-adsorption containers for 4h at 4 degrees C and the NSA was determined by HPLC. They were also dissolved in aqueous methanol or acetonitrile and the NSA to a conventional polypropylene microplate was determined. Finally, tissue culture microplates were coated with silane coupling agents and the effects of the coatings were evaluated.


RESULTS
Hydrophobic drugs (paclitaxel, verapamil and digoxin) were highly adsorbed to conventional plastic microplates, but in addition to hydrophobic drugs, positively charged drugs were well adsorbed to the tissue culture microplate. Low-adsorption microplates could reduce NSA below 15%, but positively charged or neutral hydrophobic drugs showed relatively higher adsorption. Acetonitrile showed stronger NSA inhibition than that of methanol, but the peak shapes of methotrexate and chloroquine were broadened and split. Among the silane coupling agents, GPTMS suppressed the NSA below 10%. Also, AATMS resembled the NSA pattern of GPTMS, but it increased the adsorption of methotrexate to 29%.


CONCLUSIONS
On conventional plastic microplates, NSA is mainly driven by hydrophobic interactions, but on tissue culture microplates and low-adsorption microplates, in addition to hydrophobic interactions, ionic interactions play a role in the NSA. Therefore, to reduce the NSA to plastic containers, both hydrophobic and ionic interactions should be reduced using amphiphilic organic solvents or neutral and hydrophilic coatings.
Fukazawa
Tominaga
T
Toxicology and Pharmacokinetics Laboratories, Pharmaceutical Research Laboratories, Toray Industries, Inc., 6-10-1 Tebiro, Kamakura, Kanagawa 248-8555, Japan. Tominaga_Fukazawa@nts.toray.co.jp
Yamazaki
Yuri
Y
Miyamoto
Yohei
Y
D000327:Adsorption; D001681:Biological Assay / Q000379:methods / Q000592:standards*; D004349:Drug Packaging / Q000379:methods; D004355:Drug Stability; D057927:Hydrophobic and Hydrophilic Interactions; D004364:Pharmaceutical Preparations / Q000378:metabolism*; D010969:Plastics / Q000493:pharmacokinetics*; D012821:Silanes / Q000493:pharmacokinetics; D013499:Surface Properties
D004364:Pharmaceutical Preparations; D010969:Plastics; D012821:Silanes