The present study focuses on the quality control of quinine in the compressed pharmaceutical forms circulating in eastern Democratic Republic of Congo. The analyses performed on the collected samples included disintegration of the tablets, identification of quinine in the formulations by color reaction methods and thin-layer chromatography. The quantitative analysis was performed by spectrophotometric and volumetric methods. The most significantly observed findings were abnormalities of release; underdosing, overdosing and absence of the active ingredient, Which brings us to the conclusion that more than 30% of the samples analyzed are of inferior quality and adulterated.
Malaria is a parasitic infection transmitted through the bite of plasmodium infected female anopheles mosquito, the infection causes intermittent fevers. Malaria remains the most important tropical parasites, about 300 to 500 million people are infected and claims 1.5 to 2.7 million lives per year. Almost 80% of cases are registered in sub-Saharan Africa, where most cases are children under five and pregnant women [
Artemisinin-based Combination Therapy (ACT) is exceptionally indicated for true resistance or a formal contraindication to quinine [
Quinine is an antimalarial that is the most counterfeit drug class on the planet according to the World Health Organization (WHO).
The objective of this study is to undertake control quality of quinine in the compressed pharmaceutical forms available for sale in three cities in eastern Democratic Republic of Congo (Bukavu, Goma and Uvira).
SHIMADZU UV-1280 spectrophotometer, coupled to a computer, ERWEKA-APPARATEBAU disintegration apparatus, 254 nm UV lamp of the Merck KGaA type, D-64271 Darmstadt, F.R. Germany,
Reagents and analytical grade products were used:
Concentrated sulfuric acid batch B-3901 Leuven, 6172, BELGIUM, 98%, density 1.84; Hydrochloric acid from PANREAC QUIMICA SAU, E-08211 Castellar del Valles (Barcelona), 37%, density 1.19; Ethanol 96% Vergallt MEK Carl Roth GmbH + Co.kg, 97% NaOH Extra pure LOBA CHEMIE PVT. LTD, Mumbai, Quinine Sulfate Powder from the pharmakina puré company according to the European Pharmacopoeia
This is an experimental study involving analytical comparison of 20 batches of quinine in compressed pharmaceutical form sold in South Kivu and North Kivu pharmacies and hospitals
By color reaction: We mixed each sample with 5 ml of water, then add a drop of concentrated sulfuric acid. The resulting solution was stirred, placed it in a dark room and exposed to 366 nm UV light; the observance of a stong white blue florescence indicated the presence of quinine, otherwise quinine is absent [
Preparation of sample solutions:
Preparation of the stock test solution of a 500 mg drug: a 500 mg tablet was grinded into a fine powder, then transferred into 50 ml volumetric flask. Distilled water of 5 ml was added into the flask followed by the addition of 45 ml methanol. The test solution obtained had a concentration of 10 mg/ml.
Preparation of test solution of the stock at 250 mg: we reduced a complete tablet to powdered form and extracted the powder obtained with 2 ml of water and then 23 ml of methanol using graduated pipettes and a 50 ml bottle as the test solution container of the stock.
Preparation of stock test solution at 300 mg: reduce a 300 mg tablet to a powder, pour it into a 50 ml flask and extract with 3 ml of water then 27 ml of methanol using pipettes.
Preparation of the test use test: we took 1 ml of the test solution from the stock and added 7 ml of methanol [
Quinine sulfate is a molecule possessing the chromatophore group because of its chemical structure (
The specific absorbance of quinine sulfate in 0.1 N HCl is 136 in the 1 cm long tank for a 1 g solution in 100 ml to 348 nm [
N˚ | Preparations for solutions | Concentration (mg/ml) | Dilution |
---|---|---|---|
S1 | 10 ml SM/100ml | 0.1 | 10 |
S2 | 40 ml S1/50ml | 0.08 | 12.5 |
S3 | 40 ml S2/50ml | 0.064 | 15.6 |
S4 | 25 ml S1/50ml | 0.05 | 25 |
S5 | 25 ml S3/50ml | 0.032 | 31.25 |
S6 | 20 ml S5/50ml | 0.016 | 65.5 |
Ab = Absorbance.
Assay by Alcalimetry
A quantity of powder containing quinine sulfate corresponding to 400 mg of PA was weighed and dissolved in a mixture of 10 ml of ethanol and 5 ml of chloroform, then titrated with 0.1 N sodium hydroxide in the presence of phenolphthalein. The appearance of a persistent pink color marks the end of the titration. Each ml of NaOH consumed is equivalent to 37.325 mg of quinine sulfate (C20H24N2O2)2∙H2SO4∙2H2O) [
Spectrophotometry Assay
A test portion of the powder containing 100 mg of Quinine sulfate was dissolved in 100 ml of 0.1 N HCl. After homogenization, a dilution of 5 ml in 100 ml of 0.1 N HCl was carried out, using spectrophotometer, the absorbance was read at 348 nm. The reference product was treated in the same way and under the same conditions.
Compressed dosage forms dosed at 100 mg, 250 mg, 300 mg and 500 mg quinine sulfate were the subject of this quality control work. The chipping loss was performed, 16 samples gave a loss value of less than 1% while the results of lots 7, 12, 13 and 20 were greater than 1%.
In 0.1 M HCl, all tablets disintegrated within 30 minutes except samples Nos. 3, 17, 18, 19 and 20 which broke up more than 45 minutes later.
With regard to identification tests,
Proceeding in the same way as described in the methodology (
Lot | Quinine per tablet (mg) | Crumbling (%) | Disintegration | Identification test | |
---|---|---|---|---|---|
Color reaction | Thin-layer chromotography (front report) | ||||
1 | 300 | 0.28 | 30 | − | 0.8 |
2 | 300 | 0.015 | 30 | − | 0 |
3 | 300 | 0.24 | 45 | + | 0.4 |
4 | 300 | 0.45 | 3 | + | 0.4 |
5 | 100 | 0.03 | 30 | + | 0.4 |
6 | 300 | 0.08 | 5 | + | 0.4 |
7 | 300 | 1.67 | 7 | + | 0.4 |
8 | 300 | 0.6 | 10 | + | 0.4 |
9 | 300 | 0.3 | 7 | − | 0 |
10 | 300 | 0.29 | 5 | + | 0.4 |
11 | 500 | 0.3 | 30 | + | 0.4 |
12 | 500 | 5.48 | 30 | + | 0.4 |
13 | 300 | 2.21 | 9 | + | 0.4 |
14 | 300 | 0.16 | 9 | + | 0.4 |
15 | 250 | 0.08 | 30 | + | 0.4 |
16 | 500 | 0.45 | 14 | + | 0.4 |
17 | 500 | 0.38 | 49 | + | 0.4 |
18 | 500 | 0.77 | 75 | + | 0.4 |
19 | 300 | 0.65 | 125 | − | 0.7 |
20 | 500 | 1.07 | 50 | + | 0.4 |
The results of the volumetric method are expressed in volume (average of volumes in ml) whereas those of the spectrophotometry are expressed in absorbance (average of absorbance) in
Our study was based on the quality control of twenty lots of quinine sulfate in compressed pharmaceutical forms dosed at 500 mg, 300 mg, 250 mg, 100 mg, for sale in the city of Bukavu, Goma, Uvira (Democratic Republic of Congo).
Lot | Quantification by spectrophotometry | Quantification by alkalimetry | ||
---|---|---|---|---|
Absorbance | Content ± SDS (%) | Volume consumed (ml) | Content (%) | |
1 | ||||
2 | ||||
3 | 0.67 | 101.8 ± 1.2 | 11.4 | 106.6 |
4 | 0.81 | 123.3 ± 1.1 | 13.4 | 124.5 |
5 | 0.61 | 92.7 ± 0.2 | 11.4 | 105.9 |
6 | 0.78 | 108.5 ± 1.2 | 10.5 | 97.9 |
7 | 0.62 | 94.2 ± 0.3 | 10.2 | 103.5 |
8 | 0.61 | 92.3 ± 4.6 | 11.1 | 95.2 |
9 | ||||
10 | 0.56 | 84.7 ± 0.5 | 8.5 | 78.8 |
11 | 0.64 | 96.7 ± 1.0 | 11 | 102.2 |
12 | 0.71 | 107.8 ± 1.8 | 10.5 | 97.9 |
13 | 0.6 | 91.3 ± 0.7 | 10.6 | 98.9 |
14 | 0.6 | 91.4 ± 0.5 | 10.8 | 100.3 |
15 | 0.68 | 103.09 ± 0.7 | 10 | 93.3 |
16 | 0.66 | 99.7 ± 2.0 | 10.4 | 97.05 |
17 | 0.67 | 101.6 ± 4.6 | 10.1 | 94.2 |
18 | 0.63 | 96.3 ± 7.3 | 10.1 | 93.8 |
19 | ||||
20 | 0.7 | 106.2 ± 0.1 | 10.8 | 100.2 |
Reference | 0.66 | 100 ± 0.1 | 10.95 | 102.17 ± 0.7 |
With regard to the galenic tests, the uniformity of the masses gave us the compliant results because no tablet deviated from the limit required by the European Pharmacopoeia [
Only 4 of the 20 quinine sulphate samples (20%) did not respond to the identification assay by both Quinine’s color reaction and Quinine Thin Layer Chromatography (TLC) methods. This serious anomaly can lead to therapeutic failures and even cases of intoxication In Tanzania, a simila study showed that 11% of the Quinine samples analyzed did not respond to the identification test; similarly, one conducted in three African countries [
The linearity was established by the least square regression method of the calibration curve. This standard curve was obtained over the range of concentrations from 0.016 to 0.1 mg/ml. The drawn curve gave an equation Y = 15,297X + 0.088 where the intercept and the slope are respectively 0.08 and 15.32; With a correlation coefficient (r) greater than 0.999 (
The content of active ingredient was determined for the 16 lots out of 20 possessing the active principle. Compared to the standard considered; only the content between 90% - 110% was considered to be compliant [
Counterfeiting is a practice that is in full swing in African countries; the present study focused on the quality control of quinine in pharmaceutical dosage forms. At the end of this work, our results showed that nonconformity affects different formulations of quinine tablet. Asia has held most of our samples. This counterfeiting of quinine mainly concerns overdose; underdosing and the absence of quinine in the formulations studied. The rate of non-compliance exceeds 30% of the formulations analyzed.
The authors declare no conflicts of interest regarding the publication of this paper.
Namegabe, L.M., Kadhesi, M.T., Hamuli, P.M., Mahano, A.O. and Brioen, P. (2019) Quality Control of Quinine in Pharmaceutical Forms Tablets Find East of the Democratic Republic of Congo. American Journal of Analytical Chemistry, 10, 415-422. https://doi.org/10.4236/ajac.2019.109029