HPLC methods for pharmaceutical analysis evolve from method development to commercial product testing. The majority of development and validation takes place in an R&D setting, followed by transfer to commercial sites that execute test methods on a routine basis. There is a growing need to increase confidence and probability that developed methods will be successful both during validation and long-term use with products, particularly when introducing new or unfamiliar technologies. An HPLC method pre-validation and performance prediction plan is presented using model pharmaceutical ingredients in prototype liquid formulations. The pre-validation includes limited linearity, repeatability in sample matrix, precision, carry-over, and selectivity. The performance prediction involves injecting large numbers of worst-case samples and monitoring five critical parameters: retention time, tailing factor, resolution, efficiency, and system pressure. Parameter results are assessed with respect to precision and/or system performance. In a proof of principle model, the performance prediction data demonstrate that system suitability parameters remain constant during injections of prepared samples; however, the system pressure increases over time. These underlying data indicate a potential trend prior to method validation. As a result, sample preparation and HPLC condition modifications are evaluated using pressure plots as a key performance metric.