Traces of phosgene in chloroform: Consequences for extraction of anthracyclines

Development and validation of a liquid chromatographic method for the simultaneous determination of four anthracyclines and their respective 13-S-dihydro metabolites in plasma and saliva

“…In a first step, aqueous samples adjusted to pH 3.0 (formiate buffer), 5.0 (acetate buffer), 7.0 (phosphate buffer), 9.0 (ammonium buffer) or 11.0 (carbonate buffer) were extracted in quadruplicate with each of the following solvents at a ratio of 5:1 (organic solvent: aqueous phase): pentane, hexane, ethylacetate, propylacetate, dichloromethane (ethanol stabilized), chloroform (ethanol stabilized), diethylether and t-butylmethylether. As previously demonstrated, the choice of stabilizer for halocarbons can be highly relevant [32]. Extraction with halocarbons at pH 7.0 and 9.0 gave the best results (full data in supplementary files 1 and 2).…”

Quantitative liquid chromatographic analysis of anthracyclines in biological fluids

“…More specifically, ethanol-stabilized chloroform should be preferred over non-or amylenestabilized chloroform because phosgene formation in these latter may impair anthracycline extraction and lead to artefacts [78]. Extraction under neutral or mildly alkaline conditions results in a partial recovery of glucuronic acid metabolites.…”

Solvent Derived Artifacts in Natural Products Chemistry

“…Ethanol is added to inhibit the formation of phosgene by interfering in the free radical chain reaction, whilst amylene acts as a hydrochloric acid scavenger. Recently, the consequences of the extraction of anthracyclines using chloroform stabilized with ethanol or amylene have been discussed by Maudens and colleagues and compared with the extraction using chloroform without stabilizers [43].…”