Methods and systems for delivering a liquid sample to an ion source for the generation of ions and subsequent analysis by mass spectrometry are provided herein. In accordance with various aspects of the present teachings, MS-based systems and methods are provided in which the flow of solvent into an open port sampling probe fluidly coupled to an ion source can be selectively stopped during the addition of one or more reagents into the drained open end of the sampling probe. Upon re-initiating the flow of solvent, the reagents and/or the reaction products can be delivered to the ion source. In one aspect, a method for chemical analysis is provided, the method comprising directing a flow of a first solvent from a solvent conduit to an ion source via a sampling space of a sampling probe, wherein the sampling space is at least partially defined by an open end of the sampling probe. The flow of the first solvent into the sampling space from the solvent conduit may be terminated for a first duration, and the sampling space drained. A second solvent and one or more reactants may then be added to the drained sampling space through the open end during the first duration. Thereafter, the flow of the first solvent may again be directed from the solvent conduit to the ion source via the sampling space such that the second solvent is delivered to the ion source, and such that one or more reaction products contained within the second solvent and generated by said one or more reactants may be ionized for mass spectrometric analysis.