Electrospray ionization mass spectrometry is a valuabletool in the identification and quantification of drug metabolites in biological fluids. However, there are manyinstances where matrix components present in thesefluids interfere with analyte detection and prevent theacquisition of accurate or complete results. In someinstances, the matrix can suppress ionization to such anextent that analytes are completely undetectable by MS.In this work, we investigate how ionization and ion-transfer efficiencies are affected by drastically reducingthe flow into the MS. A postcolumn concentric flow-splitting device was constructed to allow the measurementof analyte signal and ionization suppression across a rangeof flow rates (0.1-200
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L/min). Using this device, theeffects of flow rate on signal intensity and ionizationsuppression were measured in analytical experiments thatincluded flow injection analysis MS, postcolumn additionLC-MS, and on-line LC-MS analysis of metabolitesgenerated from rat liver microsomes. The device used todeliver 0.1
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L/min flows is referred to as a nanosplitterbecause it achieved high split ratios (2000:1), producingflow rates comparable to those observed in nanoelectrospray. The nanosplitter maintained chromatographic integrity with high fidelity and allowed the direct comparisonof analyte signal across a range of flow rates (0.1-200
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L/min). A significant improvement in concentration andmass sensitivity as well as a reduction in signal suppression is observed when the performance at 200 versus 0.1
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L/min flow rate is compared. Using this specially designed concentric splitting device, the advantages ofultralow flow ESI were easily exploited for applicationsemploying large bore chromatography.