No abstract

A fast quantification method for the determination of 11 antineoplastic drugs from wipe samples was developed using micro-scale liquid chromatography in combination with tandem mass spectrometry. The extraction efficiency from the wipes has been investigated using different extraction solvents. The results indicate that a mixture of 70/30 water/isopropanol (v/v) acidified with 0.1 % formic acid is suitable to desorb the antineoplastic drugs with sufficient recovery between 80 and 120 %. Compared to conventional liquid chromatography, the total analysis time can be reduced to 2.25 min using a 50 × 0.3 mm column at a flow rate of 25 μL min. Ion source parameters as well as the injection volume were optimized to ensure the highest sensitivity. The results of method validation showed an instrumental limit of quantification between 0.0068 and 0.0488 ng mL using an injection volume of 4.25 μL estimated by the signal to noise ratio. Moreover, the retention time repeatability was determined with a maximum relative standard deviation of 0.4 %. Graphical abstract Micro-LC-MS/MS separation of 11 antineoplastic drugs from wipe samples.

A novel multidimensional separation system based on online comprehensive two-dimensional liquid chromatography and hybrid high-resolution mass spectrometry has been developed for the qualitative screening analysis and characterization of complex samples. The core of the system is a consistently miniaturized two-dimensional liquid chromatography that makes the rapid second dimension compatible with mass spectrometry without the need for any flow split. Elevated temperature, ultrahigh pressure, and a superficially porous sub-3-μm stationary phase provide a fast second dimension separation and a sufficient sampling frequency without a first dimension flow stop. A highly loadable porous graphitic carbon stationary phase is employed in the first dimension to implement large volume injections that help countervailing dilution caused by the sampling process between the two dimensions. Exemplarily, separations of a 99-component standard mixture and a complex wastewater sample were used to demonstrate the performance of the dual-gradient system. In the second dimension, 30 s gradients at a cycle time of 1 min were employed. One multidimensional separation took 80-90 min (~120 min including extended hold and re-equilibration in the first dimension). This approach represents a cost-efficient alternative to online LC × LC strategies working with conventionally sized columns in the rapid second dimension, as solvent consumption is drastically decreased and analytes still are detectable at environmentally relevant concentrations.

The efficiency of miniaturized liquid chromatography columns with inner diameters between 200 and 300 μm has been investigated using a dedicated micro-liquid chromatography system. Fully porous, core-shell and monolithic commercially available stationary phases were compared applying van Deemter and kinetic plot analysis. The sub-2 μm fully porous as well as the 2.7 μm core-shell particle packed columns showed superior efficiency and similar values for the minimum reduced plate heights (2.56-2.69) before correction for extra-column contribution compared to normal-bore columns. Moreover, the influence of extra-column contribution was investigated to demonstrate the difference between apparent and intrinsic efficiency by replacing the column by a zero dead volume union to determine the band spreading caused by the system. It was demonstrated that 72% of the intrinsic efficiency could be reached. The results of the kinetic plot analysis indicate the superior performance of the sub-2 μm fully porous particle packed column for ultra-fast liquid chromatography.