The 8th Mass Spectrometry CVG Annual Symposium - Full Day Event!!!
Presentation No. 13 - Evaluation of a New Electrospray Ion Source and Interface Combination for Ruggedness and Sensitive in LC-MS/MS
George Scott; Dragan Vuckovic; Charles Jolliffe
Ionics Mass Spectrometry Group, Bolton, ON, Canada
Novel Aspect: The new method of transporting ions into a MS minimizes optimization procedure, prevents instrument contamination, and increases the sensitivity.
Introduction: The triple quadrupole mass spectrometer (MS) coupled with HPLC is a universally used technology in the pharmaceutical industry as a result of its sensitivity, ease of use, speed and robustness. One of the deficiencies of the systems today is long term robustness, often required cleaning as the result of contaminating. Most of the MS’s today have one pass of orthogonality to the entrance interface to decrease the contamination entering the MS. Here a heated interface is used with an entrance and exit orthogonal to both, which in combination with a coaxial flow ion source and low velocity flow sampling, significantly decreases the contamination, increasing long term robustness, and improves ease of use to the instrument.
Methods: A mass spectrometer with a new interface is characterized using an electrospray coupled to a tandem MS using a variety of chemical standards. The standards are used to characterize the sensitivity and signal/noise of the system with respect to: solvent flow (0.2 to 2ml/min), solvent composition (100% aqueous to 100% organic), ion source position, compound fragility, thermal sensitivity (degradation), and compound mass (mass discrimination). The parameters optimized are: position, electrospray voltage, temperature of the interface and electrospray probe, desolvation gas flow, curtain gas flow, nebulizer gas pressure and declustering voltage. A variety of matrices (10mM ammonium acetate and plasma) are used to determine the robustness of the interface via long term stability LC-MRM runs of the standard compounds.
Results: Characterizations of the following compounds are complete: acetaminophen, fluorouracil, minoxidil, testosterone, dexamethasone, salometosone, fluticasone, taurocholic acid, and reserpine with respect to sensitivity. The physical parameters explored are solvent flow and composition, ion source position and gas flows, source and interface temperatures, and the declustering potential. There is a broad optimization of the physical parameters for all the compounds tested allowing one set of values to be used for all. The only parameter which required optimization was the interface temperature (200 to 300C). As a result of the ions being transferred from atmosphere to the mass spectrometer by flow dominated regime which was very soft, the declustering voltage was the same for all compounds. This was unexpected, usually the fragile compounds or compounds with low molecular weights (<200) require a lower potential. The ease of use and roughness has been demonstrated to be a result of the unique orthogonal design of the interface source combination. The sensitivity of the compounds doubled as the solvent flow increase from 0.2 to 2 ml/min of a 1/1 water/acetonitrile. The lowest level of detection for these compounds was found to be in the 10 to 100 femtogram level.
