Abstract
Quinine- and cryptolepine-based antimalarials serve as valuable alternatives to artemisinin-based combination therapies (ACTs) in Ghana. Their use, however, is associated with adulteration and substandard quality challenges. An HPLC method targeting quinoline and indoloquinoline antimalarial alkaloids was developed, validated, and applied to evaluate herbal and pharmaceutical antimalarial formulations (HPAFs) and starting materials (APIs). The separation/quantitation of the alkaloids (including quinine, quinidine, cinchonine, cinchonidine, dihydroquinine, dihydroquinidine, and cryptolepine) was achieved on a Zorbax SB-CN column (250 mm × 4.6 mm, 5 μm), with an isocratic elution system of methanol: trifluoroacetic acid (0.1%, v/v) (15 : 85, v/v) at 1.5 mL/min and 223 nm. Method validation was according to ICH Q2(R1) guidelines. It was then used to assess the quality of APIs (n = 3) and HPAFs (n = 44) including quinine-based pharmaceutical antimalarial formulations (QBPAFs) (n = 23) and herbal antimalarial products (HAMPs). The method was found to be specific, selective, accurate, precise, and robust toward the alkaloids with linearity achieved within specified concentration ranges (r2 > 0.995 for all analytes). Analyte stability ranged between 6 and 12 hours. All the APIs contained quinine <99.0%–101.0%, with dihydroquinine and cinchonidine at levels compliant with the established acceptance criteria. The QBPAFs had quinine content ranging between 50.2% and 151.2%, with 43.5% (n = 10/23) of them complying with the acceptance criteria. The related alkaloids observed in the QBPAFs included quinidine (56.5%, n = 13/23), dihydroquinine (100%, n = 23/23), dihydroquinidine (21.7%, n = 5/23), cinchonine (17.4%, n = 4/23), and cinchonidine (95.7%, n = 22/23). For the HAMPs, 81.0% (n = 17/21) were adulterated with quinine (0.59 ± 0.04 mg/10 mL–86.03 ± 0.02 mg/10 mL). Cryptolepine was identified in 19% (n = 4/21) of the HAMPs with concentration ranging between 43.99 ± 0.43 μg/mL and 747.86 ± 0.34 μg/mL. In conclusion, the application of the ion-pair HPLC method targeting quinoline and indoloquinoline antimalarials has demonstrated the presence of quality and poor-quality HPAFs on the Ghanaian market.
Highlights
In recent years, significant progress has been made in the control of malaria on the African continent
Samples. e herbal and pharmaceutical antimalarial formulations (HPAFs) obtained for the study included APIs (n 3) (Table S1), quinine-based pharmaceutical antimalarial formulations (QBPAFs) (n 23) (Table S2), and herbal antimalarial products (HAMPs) (n 21) (Table S3). e QBPAFs and HAMPs were purchased from different outlets in Accra and Kumasi, while the APIs were donated from three different local pharmaceutical manufacturing companies
Due to the poor resolution associated with C18 and C8 columns [19], a CNbonded column was employed in this study and the results showed a good peak resolution and symmetry (Figure 1)
Summary
Significant progress has been made in the control of malaria on the African continent. Between 2000 and 2019, the incidences of malaria declined by 29% whereas deaths declined by 60%. At notwithstanding, a significant proportion of the African population continues to remain at risk to the disease. In the year 2019, out of the 229 million malaria cases and 409,000 malaria deaths reported globally, 94% of them were recorded in the African subregion. In 2020, 384,000 preventable malaria deaths were recorded in the subregion [1]. Due to the continuous-ravaging effects of malaria on human lives, there is a dedicated focus on the production of herbal and pharmaceutical antimalarial formulations (HPAFs). An increased production trend of HPAFs is observed in Sub-Saharan Africa. The production of substandard products could erode the gains made toward the fight against malaria [2]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
