Whiteness and greenness assessment with efficacy evaluation of two UPLC systems applied for the quantification of cinnarizine and dimenhydrinate along with their toxic impurities

Abstract

Fixed-dose combination of cinnarizine (CIN) and dimenhydrinate (DMH) is an effective therapy for patients diagnosed for having central and/or peripheral vestibular disorder. Comparison and evaluation of two UPLC systems for analysis of CIN and DMH along with their toxic impurities namely 1- (diphenylmethyl)piperazine (DPP) and benzophenone (BZP), respectively in pharmaceutical dosage form matrix using diode array detector (DAD) and fluorescence detector (FLD) was applied. The chromatographic conditions of UPLC systems were carried out on poroshell UPLC column C18 (3.0 × 150 mm, 1.9 μm) as a stationary phase. An isocratic elution was established using a mobile phase made of methanol and triethylamine (pH = 4.0 ± 0.02) in the ratio of (94:6, v/v). The flow rate was 0.3 mL/min using injection volume 0.5 μL through application of DAD at 256.0 nm while was done at 251.0 nm as excitation wavelength and 310.0 nm and 330.0 nm as emission wavelength for DMH and CIN in case of FLD with total run time less than 5 min. The detected linearity range for CIN was 0.5–40.0 μg/mL and that for DMH was 1.0–50.0 μg/mL using DAD while the linearity range used in FLD was 0.1–6.0 μg/mL for CIN and was 0.25–8.0 μg/mL for DMH. Different whiteness and greenness assessment tools were demonstrated to evaluate the health and safety hazard of the proposed methods such as GAPI, AGREE and RGB12 tools, as well as the chemical components risk for the mobile phase were assessed by a green specific tool named D-CHEMS-1. The two proposed UPLC systems were sustainable, green, simple, fast, and effective and were successfully used for determination of the studied drugs in their combined dosage form excluding any contribution from excipients thus, will be useful in quality control department in pharmaceutical companies.