Detection of substandard fixed-dose combination tuberculosis drugs using thin-layer chromatography
T A Kenyon1, A S Kenyon, B V Kgarebe
1The BOTUSA Project, Gaborone, Botswana. tak8@cdc.gov
Summary
Thirty-one percent of fixed-dose combination (FDC) tuberculosis (TB) drugs were substandard. Low rifampicin content, detectable by thin-layer chromatography (TLC), was a key issue in some FDCs, necessitating quality screening.
Area of Science:
- Pharmaceutical Sciences
- Medicinal Chemistry
- Public Health
Background:
- Fixed-dose combination (FDC) drugs are crucial for tuberculosis (TB) treatment adherence.
- Ensuring the quality and accurate content of FDC TB drugs is vital for effective treatment and preventing drug resistance.
- Previous quality assessments of FDC TB drugs have highlighted potential issues with drug content.
Purpose of the Study:
- To determine the actual versus stated drug content in a sample of FDC TB drugs.
- To identify substandard FDC TB drugs and characterize the nature of the sub-standardization.
- To evaluate the utility of thin-layer chromatography (TLC) as a screening method for FDC TB drug quality.
Main Methods:
- A convenience sample of 13 FDC TB drugs was analyzed.
- Chemical analysis involved thin-layer chromatography (TLC) for screening and ultraviolet (UV) spectrophotometry or liquid chromatography (LC) for confirmation.
- Substandard FDC drugs were defined as those with content outside the 85-115% range of the stated concentration.
Main Results:
- All 13 FDC TB drugs contained the stated active pharmaceutical ingredients.
- Four out of 13 (31%) FDC TB drugs were found to be substandard.
- Substandard drugs included two with low rifampicin content (15%), one with excessive rifampicin (8%), and one with excessive pyrazinamide (8%).
- FDCs with low rifampicin content failed TLC screening, while the FDC with excessive rifampicin was not detected by TLC.
- TLC demonstrated high sensitivity (100%) and specificity (90%) for detecting low rifampicin content when compared to UV spectrophotometry.
Conclusions:
- A significant proportion (31%) of FDC TB drugs in the sample were substandard, irrespective of bioavailability.
- Low rifampicin content, reliably detected by TLC, was identified in some four-drug FDC products, posing a significant concern.
- Routine quality screening of TB drugs using TLC is recommended to optimize treatment outcomes and combat acquired drug resistance.
Related Concept Videos
01:11Thin-Layer Chromatography (TLC): Overview
Thin-layer chromatography (TLC) is a chromatography technique that separates compounds based on their polarity. TLC typically uses polar silica gel, a form of silicon dioxide, as the stationary phase. The silica gel contains hydroxyl (OH) groups on its surface, which form hydrogen bonds with polar compounds, influencing their adhesion to the stationary phase.
To begin the analysis, a mixture of compounds is spotted on the starting line on the TLC plate using a thin capillary. The bottom of the...
To begin the analysis, a mixture of compounds is spotted on the starting line on the TLC plate using a thin capillary. The bottom of the...
01:26Pulmonary Tuberculosis IV
Tuberculosis, more commonly referred to as TB, is an infectious disease stemming from Mycobacterium tuberculosis. While it primarily impacts the lungs, TB can also affect other body areas. Given its severity and global impact, timely and accurate diagnosis is crucial for controlling its spread and improving patient outcomes.
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
Several diagnostic approaches are used to detect TB. The conventional method is the Tuberculin Skin Test (TST), also known as the Mantoux test. However, this method has...
01:28Pulmonary Tuberculosis V
Medical management of tuberculosis (TB) patients involves a comprehensive approach that includes diagnosis, treatment, and monitoring. The specific strategies can vary depending on the type of tuberculosis (latent or active), the patient's overall health status, and other considerations.
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the progression...
Latent tuberculosis infection occurs when TB bacteria are present in a person's body, but are not causing illness or symptoms. It is not contagious, and preventive treatment is crucial to avoid the progression...