Department of Pharmacology and Therapeutics, College of Health Sciences, Makerere University, P.O. Box 7072, Kampala, Uganda.
Department of Pharmacology, Soroti University, P.O. Box 211, Soroti, Uganda.
Malar J. 2023 May 26;22(1):165. doi: 10.1186/s12936-023-04600-8.
Substandard anti-malarial agents pose a significant challenge to effective malaria control and elimination efforts especially in sub-Saharan Africa. The quality of anti-malarials in most low-and-middle income countries (LMICs) is affected by several factors including inadequate regulation and limited resources. In this study, the pharmacopeial quality of artemether-lumefantrine (AL) in low and high malaria transmission settings in Uganda was assessed.
This was a cross-sectional study conducted among randomly selected private drug outlets. The AL anti-malarials available in drug outlets were purchased using overt method. The samples were screened for quality using visual inspection, weight uniformity, content assay and dissolution tests. The assay test was done using liquid chromatography-mass spectrometry (LC-MS). The samples were considered substandard if the active pharmaceutical ingredient (API) content was outside 90-110% range of the label claim. Dissolution test was conducted following United States Pharmacopoeia (USP) method. Data was analysed using descriptive statistics and presented as means with standard deviations, frequencies, and proportions. Correlation between medicine quality and independent variables was determined using Fisher's exact test of independence at 95% level of significance.
A total of 74 AL anti-malarial samples were purchased from high (49/74; 66.2%) and low (25/74; 33.8%) malaria transmission settings. The most common batch of AL was LONART, 32.4% (24/74), with 33.8% (25/74) being 'Green leaf'. Overall prevalence of substandard quality artemether-lumefantrine was 18.9% (14/74; 95% CI: 11.4-29.7). Substandard quality AL was significantly associated with setting (p = 0.002). A total of 10 samples (13.5%) failed artemether content assay test while, 4 samples (5.4%, 4/74) failed the lumefantrine assay test. One sample from a high malaria transmission setting failed both artemether and lumefantrine assay content test. Of the samples that failed artemether assay test, 90% had low (< 90%) artemether content. All the samples passed visual inspection and dissolution tests.
Artemether-lumefantrine agents, the recommended first-line treatment for uncomplicated malaria with APIs outside the recommended pharmacopeial content assay limit is common especially in high malaria transmission settings. There is need for continuous surveillance and monitoring of the quality of artemisinin-based anti-malarials across the country by the drug regulatory agency.
在撒哈拉以南非洲地区，劣质抗疟药物严重影响疟疾防治和消除工作的成效。在多数中低收入国家，抗疟药物的质量受到多种因素的影响，包括监管不足和资源有限。本研究评估了乌干达高低疟疾传播地区青蒿素-本芴醇（AL）的药典质量。
这是一项在随机选择的私营药店进行的横断面研究。采用公开方法从药店购买青蒿素-本芴醇抗疟药物。采用目测、重量均匀性、含量测定和溶出度试验对药物进行质量筛选。采用液相色谱-质谱联用（LC-MS）进行含量测定。如果活性药物成分（API）含量超出标签声称的 90-110%范围，则认为药物为劣药。溶出度试验按照美国药典（USP）方法进行。采用描述性统计方法对数据进行分析，结果表示为均值±标准差、频率和比例。采用 Fisher 确切概率检验评估药物质量与独立变量之间的相关性，检验水准为 95%。
共从高（49/74；66.2%）和低（25/74；33.8%）疟疾传播地区购买了 74 份 AL 抗疟药物样本。最常见的 AL 批次为 LONART，占 32.4%（24/74），其中 33.8%（25/74）为“绿叶”。不合格的青蒿素-本芴醇药物总体比例为 18.9%（14/74；95%CI：11.4-29.7）。药物质量与设置显著相关（p=0.002）。共有 10 份样本（13.5%）的青蒿素含量测定试验不合格，4 份样本（5.4%，4/74）的本芴醇含量测定试验不合格。一份来自高疟疾传播地区的样本同时未能通过青蒿素和本芴醇含量测定试验。在青蒿素含量测定试验不合格的样本中，90%的样本青蒿素含量低于 90%。所有样本均通过了目测和溶出度试验。
在青蒿素-本芴醇作为无并发症疟疾一线治疗药物的地区，API 超出推荐药典含量测定范围的情况较为常见，尤其是在疟疾高传播地区。药品监管机构需要持续监测全国青蒿素类抗疟药物的质量。
