Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles
A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC<sup>®</sup>) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analy...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/21/6597 |
| _version_ | 1797512032549863424 |
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| author | Jesús Alberto Afonso Urich Viktoria Marko Katharina Boehm Raymar Andreína Lara García Dalibor Jeremic Amrit Paudel |
| author_facet | Jesús Alberto Afonso Urich Viktoria Marko Katharina Boehm Raymar Andreína Lara García Dalibor Jeremic Amrit Paudel |
| author_sort | Jesús Alberto Afonso Urich |
| collection | DOAJ |
| description | A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC<sup>®</sup>) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50–6.50 µg/mL (R<sup>2</sup> = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs. |
| first_indexed | 2024-03-10T05:56:10Z |
| format | Article |
| id | doaj.art-c5c7ac1c3ef7426292f13b5334493a9a |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T05:56:10Z |
| publishDate | 2021-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-c5c7ac1c3ef7426292f13b5334493a9a2023-11-22T21:23:41ZengMDPI AGMolecules1420-30492021-10-012621659710.3390/molecules26216597Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD PrinciplesJesús Alberto Afonso Urich0Viktoria Marko1Katharina Boehm2Raymar Andreína Lara García3Dalibor Jeremic4Amrit Paudel5Research Center Pharmaceutical Engineering GmbH, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH, 8010 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH, 8010 Graz, AustriaDepartment of Health Studies-Biomedical Science, FH JOANNEUM, 8020 Graz, AustriaResearch Center Pharmaceutical Engineering GmbH, 8010 Graz, AustriaA novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC<sup>®</sup>) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50–6.50 µg/mL (R<sup>2</sup> = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs.https://www.mdpi.com/1420-3049/26/21/6597hexoprenalineanalytical quality by design (AQbD)design of experimentstability-indicating methodultra-performance liquid chromatography |
| spellingShingle | Jesús Alberto Afonso Urich Viktoria Marko Katharina Boehm Raymar Andreína Lara García Dalibor Jeremic Amrit Paudel Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles Molecules hexoprenaline analytical quality by design (AQbD) design of experiment stability-indicating method ultra-performance liquid chromatography |
| title | Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles |
| title_full | Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles |
| title_fullStr | Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles |
| title_full_unstemmed | Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles |
| title_short | Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles |
| title_sort | development and validation of a stability indicating uplc method for the determination of hexoprenaline in injectable dosage form using aqbd principles |
| topic | hexoprenaline analytical quality by design (AQbD) design of experiment stability-indicating method ultra-performance liquid chromatography |
| url | https://www.mdpi.com/1420-3049/26/21/6597 |
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