Since the outbreak of the global COVID-19 pandemic, the potential for liquid chromatography- tandem mass spectrometry (LC-MS/MS) analyses of SARS-CoV-2 peptides to provide complementary and supplemental testing to established quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays has been extensively explored. However, matching the throughput and sensitivity of qRT-PCR has proven challenging. High performance instrumentation and low flow rates are necessary for detection of positive samples with low viral loads, but lower flow rates generally result in longer analysis times. An additional consideration that is often overlooked in publications discussing LC-MS/MS analyses of SARS-CoV-2 is carry-over of peptides from samples with high viral loads. In this work, we describe our evaluation of numerous platforms for optimal detection of SARS-CoV-2 peptides.