Assessment of the Quality of Injectable Antibiotics in Benin

Abstract

Substandard and falsified medicines are an enormous threat to global health. Poor quality antibiotic preparations contribute to the development of antimicrobial resistance. In surgery, where the occurrence of healthcare-associated infections is high, healthcare teams need to rely on the quality of antibiotic prophylaxis to prevent infections. We assessed the quality of antibiotics used for surgical infection prophylaxis in Benin. Thirty-three samples were collected from six hospitals located in various departments in Benin. The antibiotics (powders for injection: amoxicillin + clavulanic acid, ampicillin, ceftriaxone; solutions for injection: ciprofloxacin, gentamicin, metronidazole) were assessed using visual inspection, pharmacotechnical tests (including uniformity of mass, pH measure, sterility test, and active pharmaceutical ingredient identification), and assay tests (including a simple analytical method thin layer chromatography) and complex analytical techniques (ultraviolet-visible spectrophotometry, high-performance liquid chromatography-diode-array detection, conductometry). Because the material needed for the methods recommended by the pharmacopeias to assess the dosage of gentamicin was not available, we developed and validated a conductometry method. Results showed that 97% (n = 32) of the samples passed visual inspection; 100% (n = 33) of the samples passed the pharmacotechnical tests, identification of active ingredients, and sterility test; 88% (n = 29) passed the test for percentage of active pharmaceutical ingredients. Overall, 15% of the samples did not pass the quality test (3% on visual inspection and 12% for excess active ingredients). Although most of the samples passed the quality tests, it appears important to perform routine quality control for intravenous medicines.

Figure 1.

Typical chromatograms of amoxicillin and clavulanic acid chromatographic pics of clavulanic acid (1A) and amoxicillin (2A) in reference solution at 220 nm. Chromatographic pics of clavulanic acid (1B) and amoxicillin (2B) in sample solution coded E1 at 220 nm. This figure appears in color at www.ajtmh.org.

Figure 2.

Typical chromatograms of four antibiotics chromatographic pics of clavulanic acid (1A) and amoxicillin (2A) in sample solution coded E1 monitored at 220 nm. Chromatographic pic of ampicillin (1B) in a sample solution coded E5 monitored at 254 nm. Chromatographic pic of ciprofloxacin (1C) in a sample solution coded E5 monitored at 278 nm. Chromatographic pic of metronidazole (1D) in a sample solution coded E5 monitored at 319 nm. This figure appears in color at www.ajtmh.org.

Figure 3.

Accuracy profile obtained by using linear regression model. The plain red line is the relative bias, the dashed blue lines are the β-expectation tolerance limits, and the dashed black lines represent the acceptance limits. The dots represent the relative error of the back-calculated concentrations and are plotted with respect to their targeted concentration. This figure appears in color at www.ajtmh.org.