Stability Indicating LC Method Development for Hydroxychloroquine Sulfate Impurities as Available for Treatment of COVID-19 and Evaluation of Risk Assessment Prior to Method Validation by Quality by Design Approach

Abstract

A quality by design-based stability indicating HPLC method has been developed for hydroxychloroquine sulfate impurities. The optimized HPLC method can detect and quantify the hydroxychloroquine sulfate and related organic impurities in pharmaceutical solid oral dosage forms. Nowadays, for the quantification of impurities in drug products demands more comprehensive way of analytical method development. The quality by design approach allows the assessment of different analytical parameters and their effects with minimum number of experiments. A highly sensitive and stability indicating RP-HPLC method was developed and evaluated the risk assessment prior to method validation. The chromatographic separation was achieved with X-terra phenyl column (250 × 4.6 mm, 5 µm) using phosphate buffer (0.3 M and pH 2.5). The gradient method flow rate was 1.5 mL min −1 and UV detection was made at 220 nm. The calibration curve of hydroxychloroquine sulfate and related impurities were linear from LOQ to 150% and correlation coefficient was found more than 0.999. The precision and intermediate precision % RSD values were found less than 2.0. In all forced degradation conditions, the purity angle of HCQ was found less than purity threshold. The optimized method found to be specific, accurate, rugged, and robust for determination of hydroxychloroquine sulfate impurities in the solid oral dosage forms. Finally, the method was applied successfully in quality control lab for stability analysis.

A simple alternative and improved HPLC method for the estimation of doravirine, lamivudine, and tenofovir disoproxil fumarate in solid oral dosage form

“…Doravirine, lamivudine, and tenofovir disoproxil fumarate were stable under forced photolytic and neutral degradations. In the degradation studies, peak purity test results derived from the photodiode-array detector (Dongala et al, 2020) confirmed that the peaks of doravirine, lamivudine, and tenofovir disoproxil fumarate were homogeneous and pure in all the analyzed stress samples. The stressed samples results are presented in Table 7.…”

“…The stability studies were conducted by exposing the dosage form to different stress conditions such as acid, base, peroxide, thermal, light, and water (Dongala et al, 2019;Katakam & Dongala, 2020a,b). The dosage form was slightly degraded in acid, base, peroxide, and thermal conditions, but remained stable in photolytic and hydrolytic conditions.…”

A validated stability‐indicating reversed‐phase‐HPLC method for dipyridamole in the presence of degradation products and its process‐related impurities in pharmaceutical dosage forms

“…At the end of each period in each test, degraded samples were tested and reviewed. None of the samples degraded in any of the studies (Dongala et al, 2019(Dongala et al, , 2020Naresh et al, 2020). The forced degradation results are shown in Table 3.…”

A validated eco-friendly HPLC-FLD for analysis of the first approved antiviral remdesivir with other potential add-on therapies for COVID-19 in human plasma and pharmaceuticals

“…23 Also, HCQ and LVX have been described as a combination treatment in cutaneous manifestations in patients with COVID-19. Numerous HPLC [25][26][27][28][29][30][31][32][33][34][35] and spectrouorimetric 36 studies have been reported to analyze each cited drug alone or with other drugs. Till now, only two HPLC methods 34,35 and one spectro-uorimetric method 36 have been reported to determine two of the mentioned drugs, RDV and HCQ, together.…”