Could fluorinated pharmaceuticals have an impact on the EOF amount in human blood?

Sammanfattning: Recent studies have discovered an increasing amount of unknown organofluorine in human blood. This increase insinuate that humans might be exposed to potentially new and unidentified organofluorine compounds. Currently there is a large gap between the amount of per- and polyfluorinated substances (PFAS) being monitored and the number of PFAS existing. Due to regulations of legacy PFAS like perfluorooctanoic acid (PFOA) and perfluorooctane sulfonic acid (PFOS), production have shifted to new PFAS, mainly short-chains (C4-C6). New approaches have been made in order to discover these emerging PFAS, for example total oxidizable precursor (TOP) assay and extractable organofluorine (EOF) analysis. Though, these methods are non-specific and therefore useful in screening of fluorinated compounds. In today’s pharmaceutical market, a lot of drugs contain fluorine, and there is a current increase in number of fluorinated pharmaceuticals. Since EOF analysis measures all organofluorine that can be extracted, the presence of fluorinated pharmaceuticals in a sample may contribute to the EOF amount. However, if fluorinated pharmaceuticals do co-extract during sample preparation for common PFAS analysis is not yet known. This study evaluates if selected pharmaceuticals (fluoxetine, seproxetine, celecoxib and ciprofloxacin) will be co-extracted during ion pair extraction, a common extraction for EOF analysis. The extraction was first optimized in order to gain a good extraction efficiency for the pharmaceuticals. Ion pair solution adjusted to different pH’s (pH 3-4, pH 10 and pH 12) was tested, celecoxib had a good recovery independent of what pH was used (95%-102%), fluoxetine and seproxetine were only extractable at high pH’s (10 and 12) and had a recovery of around 90%, ciprofloxacin, however, could not be extracted no matter a low or high pH. The extraction was then conducted both with a pH of 10 and with a low pH (3-4) on human sera samples (n=6); the sera samples included 3 samples where subjects had been taking fluoxetine and 3 control samples. When analysis of the extracted sera samples was performed, no detectable level of pharmaceutical including its known metabolite seproxetine was found. An EOF and TF analysis of the sera samples were also performed. The EOF analysis could however not indicate any presence of pharmaceutical due to contamination in the procedural blanks. The TF analysis indicated vaguely a higher amount of total fluorine in the sera samples where subjects had taken fluoxetine compared to the control group; however, the large variation between the two groups make it hard to draw any conclusion. Since fluoxetine, seproxetine and celecoxib could be extracted when spike tests were performed, hypothetically they could contribute to the EOF amount. However, since no detectable level was found in the sera samples after extraction it cannot be stated for sure that these pharmaceuticals can be extracted from human blood, using ion-pair extraction. The unanswered question here is if the pharmaceutical is present in some other form in the sera samples, which cannot be extracted, or if it is even present at all.