A multipurpose eco-friendly separation-based approach for appraisal of a single-pill triple-action cramp relief combination; impurity separation, dissolution study and greenness/whiteness assessment

[Display omitted] •A triple-action cramp relief over-the-counter pharmaceutical formulation of paracetamol, caffeine and pyrilamine maleate.•Novel eco-friendly HPTLC-densitometry and HPLC-UV methods for mixture analysis and purity assessment.•Successful applicability in assaying and quality control of the market tablets.•Dissolution profiling of Midol® Complete caplets as an in-vivo efficiency indicator.•Affirming methods sustainability via implementing various greenness and whiteness assessment tools. Over the years, several single-pill combinations have been produced and utilized as an alternative option for treatment of the signs and symptoms ofPrimary dysmenorrhea. The presence of multiple drugs together poses a challenge for analysts regarding analysis, making it a significant hurdle to overcome. A combination of paracetamol (PAR), caffeine (CAF), and pyrilamine maleate (PYR) is commonly recommended as an over-the-counter triple-action treatment to alleviate mild to moderate premenstrual syndrome symptoms. This study presented two liquid chromatographic methods that simultaneously determine PAR, CAF, and PYR in Midol® Complete caplets along with three officially recognized impurities, namely, p-aminophenol, theophylline, andp-anisaldehyde. The initial approach employed high-performance thin-layer chromatography alongside a densitometric scanning technique. The experimental setup utilized silica gel HPTLC plates as the stationary phase, and ethyl acetate: aqueous ammonium hydroxide (10.0:0.1, v/v) mixture as the developing system. The densitometric scanning was conducted at a wavelength of 210.0 nm. The second approach, developing high-performance liquid chromatographic method coupled with ultraviolet detection. Inertsil ODS-3 C18 column (250 × 4.6 mm, 5 μm) was used to separate the six compounds effectively. For the experimental procedure, an isocratic elution method was chosen with a mobile phase consisting of a mixture of 0.02 M potassium dihydrogen phosphate buffer acidified with o-phosphoric acid (pH 3.0), and methanol (80:20, v/v) at a flow rate of 1.0 mL/min. UV detection was carried out at a wavelength of 210.0 nm. The two proposed methods have been validated in accordance with ICH recommendations. In addition, the suggested HPLC-UV technique was used to track the release profile of the cited drugs during the in-vitro study. The developed methods were assessed and compared for their environmental impact using various greenness evaluation tools.