Targeted and untargeted headspace gas chromatography-mass spectrometry methods for the ex vivo characterization of silicone oil tamponades used in ophthalmic surgery

Due to their transparency, inertness, and high interfacial tension with water, silicone oils (SOs) are widely used as long-term intraocular tamponade to treat cases of retinal detachment [1]. Different medical grade SOs having molecular weights in the 1000-5000 mPa.s range [2] are used for ophthalmic surgery. They are mainly constituted of mixtures of linear polydimethylsiloxane polymers having different chains length and may contain linear and cyclic species of lower molecular weights as by-products of oil polymerization. Unfortunately, unexpected and not fully explained central visual loss in vitrectomized eyes with silicone oil tamponade is a severe complication of this surgical procedure [3]. In this study, an untargeted headspace-gas-chromatography-mass spectrometry (HS-GC-MS) method was developed to identify low molecular weight contaminants in three different types of silicone oil tamponades, namely Siluron 2000, RS-OIL ECS5000 and Densiron Xtra. Both commercial and post-operative tamponades were analysed to screen for the different classes of compounds present in the samples. The most abundant classes were short-chain siloxanes, fluorinated compounds, and linear and branched hydrocarbons. To quantify the siloxanes present in the samples, a targeted HS-GC-MS method was optimized using a Box-Wilson Central Composite Design followed by the multicriteria method of desirability functions [4]. A global desirability D = 0.91 was calculated in correspondence to an extraction temperature and an extraction time of 100 °C and 20 min, respectively. The method was validated according to the Bioanalytical Method Validation guidelines [5] and applied for the analysis of 41 patients according to the different type of tamponade used. High sensitivity with limits of quantification in the low μg/L range, good precision with RSD% <12 % and accuracy with recovery rates in the 81(±7)–96(±4) % range were achieved. Short-chain siloxanes were quantified in both commercial and post-operative tamponades, being the RS-OIL ECS5000 characterized by the highest concentration levels of the investigated analytes. By contrast, Densiron Xtra tamponades showed the lowest amount of short-chain siloxanes, observing a general decrease in their concentration levels according to the residence time in the eyes. Considering that for some compounds an inverse correlation was found between their concentration in the in vivo samples and the residence time in patients’eyes of patients, these findings can provide useful information to define a risk profile associated with the use of different tamponades.