Titrimetric determination of Cremophor EL in aqueous solutions and biofluids: part 2: ruggedness of the method with respect to biofluids.

A titration method for Cremophor EL, as a multicomponent mixture commonly used as non-ionic emulgent for manufacturing certain parenteralia, was developed for quantitative routine analysis in biofluids. A coated wire electrode is used as the end-point indicator in potentiometric titrations of Cremophor EL with sodium tetraphenylborate. The method tolerates a broad pH range, addition of alkanols and components of drug formulations and is sufficiently rugged. Reliable results are obtained at 20 degrees C. Disturbing ions from biofluid matrices can be masked or complexed by addition of formaldehyde, ethylenediaminetetraacetic acid and sodium fluoride. Sodium hydroxide is used for the required adjustment of the samples to pH 10. Cremophor EL spiked urine samples can be determined directly, whereas the true value of the emulgent content in the case of Cremophor EL spiked plasma samples is achieved by means of a conventional method.