In order to simultaneously quantify the residues of the active pharmaceutical ingredients (API) lisinopril and hydrochlorothiazide (HCT) in cleaning control samples taken from pharmaceutical manufacturing equipment surfaces after manufacturing of lisinopril/hydrochlorothiazide 20/25 mg uncoated tablets, this study developed and validated direct swab and indirect rinse sampling procedures. To achieve an appropriate and good recovery (>80%), the swab and rinse sample processes were created and validated. Pharmacological and toxicological standards have been used to define the acceptability limits for the aforementioned APIs on the surfaces of industrial equipment. For the simultaneous quantitative analysis of lisinopril and HCT residues, a new, quick, specific, and selective HPLC technique was developed. This approach was verified in terms of robustness, system suitability test, specificity, linearity-range, precision, and limits of detection and quantitation. Additionally, the compatibility of membrane filters and the stability of API solutions were investigated. The method validation was completed in accordance with the US Pharmacopeia's standards and the ICH Q2 guidelines. Lisinopril's limit of detection and quantitation were 0.039 µg/ml and 0.155 g/mL, respectively, while HCT's were 0.012 g/mL and 0.025 g/mL