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The pH dependence of the aqueous solubility of morphine, fentanyl, and sufentanil was investigated at 35°C. Dissociation constants and corresponding pKa′ values of the drugs were obtained from measured free-base solubilities (determined at high pH's) and the concentrations of saturated solutions at intermediate pH's. Morphine, fentanyl, and sufentanil exhibited pKa′ values of 8.08, 8.99, and 8.51,...
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