Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis
Drug products used for treating tuberculosis are one of the most widely reported medicines to be classified as falsified or substandard in low- and middle-income countries, representing a major hazard to health. The aim of this study was, firstly, to develop an ultra-performance liquid chromatograph...
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| Format: | Article |
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MDPI AG
2022-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/20/7141 |
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| author | Javier Suárez-González Amor R. Cáceres-Pérez Alexis Oliva Ana Santoveña-Estévez José B. Fariña |
| author_facet | Javier Suárez-González Amor R. Cáceres-Pérez Alexis Oliva Ana Santoveña-Estévez José B. Fariña |
| author_sort | Javier Suárez-González |
| collection | DOAJ |
| description | Drug products used for treating tuberculosis are one of the most widely reported medicines to be classified as falsified or substandard in low- and middle-income countries, representing a major hazard to health. The aim of this study was, firstly, to develop an ultra-performance liquid chromatography (UPLC) method which is able to analyze fixed combination tablets with up to four active pharmaceutical ingredients, including isoniazid, pyrazinamide, rifampicin, and ethambutol. Secondly, we aimed to optimize it through the design of experiments and multi-linear regression based on a central composite design and to validate it according to the guidelines of the International Conference on Harmonization. The application of this tools enabled the identification of the influential factors (flow rate, formic acid, and temperature) and their effects on the studied responses (retention factor and percentage for each drug) as part of the quality by design approach. The method proved to be to be linear in the range from 5.0 to 15 µg/mL for isoniazid, pyrazinamide, and rifampicin, being precise (<1%) and accurate (97–101%). In addition, the method validated for ethambutol proved to be linear from 1.4 to 4.2 µg/mL, as well as precise (0.54%) and accurate (97.3%). The method was stability indicated for all the active pharmaceutical ingredients studied and was able to detect two substandard formulations sampled on the African market. |
| first_indexed | 2024-03-09T19:41:54Z |
| format | Article |
| id | doaj.art-f087b76131b640bfbf596611d09d36d2 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T19:41:54Z |
| publishDate | 2022-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-f087b76131b640bfbf596611d09d36d22023-11-24T01:38:14ZengMDPI AGMolecules1420-30492022-10-012720714110.3390/molecules27207141Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat TuberculosisJavier Suárez-González0Amor R. Cáceres-Pérez1Alexis Oliva2Ana Santoveña-Estévez3José B. Fariña4Departamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, SpainDepartamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, SpainDepartamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, SpainDepartamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, SpainDepartamento de Ingeniería Química y Tecnología Farmacéutica, Facultad de Farmacia, Universidad de La Laguna, 38200 San Cristóbal de La Laguna, SpainDrug products used for treating tuberculosis are one of the most widely reported medicines to be classified as falsified or substandard in low- and middle-income countries, representing a major hazard to health. The aim of this study was, firstly, to develop an ultra-performance liquid chromatography (UPLC) method which is able to analyze fixed combination tablets with up to four active pharmaceutical ingredients, including isoniazid, pyrazinamide, rifampicin, and ethambutol. Secondly, we aimed to optimize it through the design of experiments and multi-linear regression based on a central composite design and to validate it according to the guidelines of the International Conference on Harmonization. The application of this tools enabled the identification of the influential factors (flow rate, formic acid, and temperature) and their effects on the studied responses (retention factor and percentage for each drug) as part of the quality by design approach. The method proved to be to be linear in the range from 5.0 to 15 µg/mL for isoniazid, pyrazinamide, and rifampicin, being precise (<1%) and accurate (97–101%). In addition, the method validated for ethambutol proved to be linear from 1.4 to 4.2 µg/mL, as well as precise (0.54%) and accurate (97.3%). The method was stability indicated for all the active pharmaceutical ingredients studied and was able to detect two substandard formulations sampled on the African market.https://www.mdpi.com/1420-3049/27/20/7141tuberculosisdesign of experimentmulti-linear regressioncentral composite designquality by design |
| spellingShingle | Javier Suárez-González Amor R. Cáceres-Pérez Alexis Oliva Ana Santoveña-Estévez José B. Fariña Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis Molecules tuberculosis design of experiment multi-linear regression central composite design quality by design |
| title | Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis |
| title_full | Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis |
| title_fullStr | Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis |
| title_full_unstemmed | Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis |
| title_short | Development and Optimization of a New UPLC-UV/MS Method through DoE and MLR for Detecting Substandard Drug Products to Treat Tuberculosis |
| title_sort | development and optimization of a new uplc uv ms method through doe and mlr for detecting substandard drug products to treat tuberculosis |
| topic | tuberculosis design of experiment multi-linear regression central composite design quality by design |
| url | https://www.mdpi.com/1420-3049/27/20/7141 |
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