Like many small molecule drugs, chloroquine phosphate (Figure 1), an effective anti-malarial, was investigated as a potential therapy to the novel coronavirus. While current clinical evidence does not appear to support the use of hydroxychloroquine or chloroquine for hospitalized SARS-CoV-2 infected patients, Waters began examining improved analytical methods during the early stages of the COVID-19 pandemic. This application brief offers a quick HPLC-UV method with MS compatible conditions for chloroquine phosphate analysis. Mass spectroscopy (MS) allows the investigator to accurately identify new or unknown components that may develop during the formulation process or routine testing. The new method offers higher resolution, less tailing, and faster run times compared to the current USP Monograph for chloroquine phosphate tablets (USP42-NF37). Regardless of the final clinical outcome for chloroquine in the context of COVID-19, these analytical advances are still applicable for chloroquine analysis generally. Additionally, this work may be transferrable in part for other small molecule therapies.