Fighting Poor Quality Medicines: Development, Transfer and Validation of Generic HPLC Methods for Analyzing Two WHO Recommended Antimalarial Tablets

Abstract

As serious but neglected public health problems, poor quality medicines, i.e. for antimalarial medicines, urged to be fought. One of the approaches is to consider the analytical chemistry and separative techniques. In this study, a generic liquid chromatographic method was firstly developed for the purpose of screening 8 antimalarial active ingredients, namely amodiaquine (AQ), piperaquine (PPQ), sulfalene (SL), pyrimethamine (PM), lumefantrine (LF), artesunate (AS), artemether (AM) and dihydroartemisinine (DHA) by applying DoE/DS optimization strategy. Since the method was not totally satisfying in terms of peak separation, further experiments were undergone applying the same development strategy while splitting the 8 ingredients into five groups. Excellent prediction was observed prior to correlation between retention times of predicted and observed separation conditions. Then, a successful geometric transfer was realized to reduce the analysis time focusing on the simultaneous quantification of two WHO's recommended ACTs in anti-malarial fixed-dose combination (AM-LF and AS-AQ) in tablets. The optimal separation was achieved using an isocratic elution of methanol-ammonium formate buffer (pH 2.8; 10 mM) (82.5:17.5, v/v) * These authors have equally contributed to this article. # Corresponding author. J. K. Mbinze et al.128 at 0.6 ml/min through a C18 column (100 mm × 3.5 mm, 3.5 μm) thermostated at 25˚C. After a successful validation stage based on the total error approach, the method was applied to determine the content of AM/LF or AS/AQ in seven brands of antimalarial tablets currently marketed in West, Central and East Africa. Satisfying results were obtained compared to the claimed contents.

Green Analytical Methods of Antimalarial Artemether-Lumefantrine Analysis for Falsification Detection Using a Low-Cost Handled NIR Spectrometer with DD-SIMCA and Drug Quantification by HPLC

“…Moreover, ion-pair reagents most often drastically increase the equilibration time of the chromatographic column, leading to a high consumption of mobile phases and long analysis times. In the literature, there are some publications about the simultaneous HPLC analysis of AL in formulations [22][23][24][25][26][27]. However, they have not been developed according to the green analytical chemistry principles.…”

Simple LC Isocratic Methods Development, Validation, and Application in the Analysis of Poor Quality Antimalarial Medicines

“…Artemether/Lumefantrine in Tablet Formulations Reference to the USP, International and European pharmacopoeias allowable adjustments in chromatographic systems [13] [14] [15], our previously validated method for the analysis of artemether/lumefantrine in tablets forms [16] was adjusted in order to reduce the analysis time and increase the sample analysis throughput. The following solutions were prepared:…”

“…Artemether/Lumefantrine in Tablet Formulations Our former analytical method for the analysis of artemether/lumefantrine in tablet formulations [16] was readjusted to improve the analysis time (run time), and sample treatment by increasing the capacity of methanol in dissolving lumefantrine. Hence, to improve the analysis time, we slightly increased the proportion of methanol in the mobile phase and the run time reduced; then, to increase the capacity of methanol in dissolving lumefantrine, we slightly increased the acidity power by using methanol acidified with phosphoric acid 0.2% (w/v) instead of 0.1% (w/v) previously used.…”

“…Our earlier developed method in isocratic mode for the analysis of artemether and lumefantrine in tablet forms [16] was adjusted by improving the dissolution capacity of methanol on lumefantrine and therefore allowing to speed up the Hence, from the original method that had a run time of 16 minutes, we adapted the mobile phase proportions to 85:15, v/v of methanol and ammonium formate buffer pH 2.8 respectively, 0.7 mL min −1 of flow rate, and 25˚C of column oven using a Zorbax-Extend C18, 80Å, 100 × 4.6 mm (dp: 3.5 µm) analytical column. This allowed to reduce the analysis time from 16 min to 6 minutes on a 100 × 4.6 mm column as illustrated in Figure 5, and to 10 minutes on 150 × 4.6 mm columns with the possibility to reduce the run time by changing the flow rate to 1.0 mL min −1 with the same mobile phase.…”

Green reversed‐phase HPLC development strategy: Application to artesunate and amodiaquine analysis

“…However, this reagent may stick to the columns and may only be removed after extensive flushing procedures, consuming high volumes of mobile phase and time, which is contrary to green chemistry principles. In the literature, there are some publications about the simultaneous HPLC analysis of AS and AQ in formulations [21][22][23][24], but they have not been developed according to GAC criteria. Also, AQ peak appears asymmetrical except in one publication where an ion-pairing agent (octanesulfonate) was added to improve AQ peak shape [23].…”