Abstract:
Quinine- and cryptolepine-based antimalarials serve as valuable alternatives to artemisinin-based combination therapies (ACTs)
in Ghana. *eir 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). *e separation/quantitation of the alkaloids (including quinine,
quinidine, cinchonine, cinchonidine, dihydroquinine, dihydroquinidine, and cryptolepine) was achieved on a Zorbax SB-CN
column (250mm× 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). *e 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. *e QBPAFs had quinine content ranging between 50.2% and 151.2%, with 43.5% (n = 10/23) of
them complying with the acceptance criteria. *erelated 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.
