Due to the COVID-19 pandemic, disinfectant use increased across community settings, including schools. The increased potential for exposure to disinfectants raises questions regarding possible subsequent health effects. Although there are standardized methods for measuring many disinfectants, such as ethanol, there are no consensus sampling and analytical methods for quaternary ammonium compounds (QACs). Disinfectants, with active ingredients including QACs and ethanol, may be applied to hard surfaces such as floors and countertops through spraying and wiping surfaces, and may also be applied via a “spray-and-leave” approach, depending on manufacturer’s instructions for use. Due to the wide range of applications, the contact time can vary significantly based on product formulation and concentration. Thus, a series of studies were conducted to verify that air and surface sampling and analytical methods identified from the published literature can detect and measure QACs on surfaces and in air at exposure concentrations relevant for use scenarios in a classroom environment. Sampling was conducted in a controlled laboratory and in a school setting. The exposure conditions were designed to mimic a child’s exposure following disinfecting of a class room desk. A QAC-based disinfectant spray containing four different QAC congeners was selected as the representative QAC product, and an ethanol-based disinfectant spray was also used. Ethanol concentrations were measured in air, but not surfaces, due to volatility. Overall, this study demonstrated the viability of sampling and analytical methods for measuring and evaluating inhalation, dermal, and surface exposures to disinfectants containing QACs. Measurable concentrations of QACs were detected in all surface samples and some, but not all, of the air samples. Concentrations of ethanol and QACs measured in air were much lower than relevant health-based exposure limits, and therefore there is no expected risk of adverse effects to the bystander from proper (as-instructed) use of either product in a school setting. Risk from cumulative exposures with dermal, oral, and multi-route exposures were not quantified. Evaluation of such exposures and testing of additional scenarios would add to the extant literature for product safety assessment.