Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer
<i>Background and Objectives:</i> Ceritinib (CER) is a potent drug of the third-generation tyrosine kinase inhibitor class. CER has been approved for the treatment of patients with non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase (ALK) mutation gene. In the lit...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-10-01
|
| Series: | Medicina |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1648-9144/59/10/1813 |
| _version_ | 1797573021647503360 |
|---|---|
| author | Reem M. Abuhejail Nourah Z. Alzoman Ibrahim A. Darwish |
| author_facet | Reem M. Abuhejail Nourah Z. Alzoman Ibrahim A. Darwish |
| author_sort | Reem M. Abuhejail |
| collection | DOAJ |
| description | <i>Background and Objectives:</i> Ceritinib (CER) is a potent drug of the third-generation tyrosine kinase inhibitor class. CER has been approved for the treatment of patients with non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase (ALK) mutation gene. In the literature, there is no green and high-throughput analytical method for the quantitation of CER in its dosage form (Zykadia<sup>®</sup> capsules). This study describes, for the first time, the development and validation of two novel one-step and green microwell spectrophotometric methods (MW-SPMs) for the high-throughput quantitation of CER in Zykadia<sup>®</sup> capsules. <i>Materials and Methods:</i> These two methods were based on an <i>in microwell</i> formation of colored derivatives upon the reaction of CER with two different benzoquinone reagents via two different mechanisms. These reagents were <i>ortho</i>-benzoquinone (OBQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and their reactions proceeded via condensation and charge transfer reactions, respectively. The reactions were carried out in 96-well transparent plates, and the absorbances of the colored reaction products were measured with an absorbance microplate reader at 540 and 460 nm for reactions with OBQ and DDQ, respectively. The optimum conditions of reactions were established, their molar ratios were determined, and reaction mechanisms were postulated. Under the refined optimum reaction conditions, procedures of MW-SPMs were established and validated according to the guidelines of the International Council on Harmonization. <i>Results:</i> The limits of quantitation were 6.5 and 10.2 µg/well for methods involving reactions with OBQ and DDQ, respectively. Both methods were applied with great reliability to the determination of CER content in Zykadia<sup>®</sup> capsules and their drug uniformity. Greenness of the MW-SPMs was evaluated using three different metric tools, and the results proved that the two methods fulfil the requirements of green analytical approaches. In addition, the simultaneous handling of a large number of samples with microvolumes in the proposed methods gave them the advantage of a high-throughput analysis. <i>Conclusions</i>: The two methods are valuable tools for rapid routine application in pharmaceutical quality control units for the quantitation of CER. |
| first_indexed | 2024-03-10T21:03:30Z |
| format | Article |
| id | doaj.art-62f3e5b1f9644beba8bd9fa5b5dd3567 |
| institution | Directory Open Access Journal |
| issn | 1010-660X 1648-9144 |
| language | English |
| last_indexed | 2024-03-10T21:03:30Z |
| publishDate | 2023-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Medicina |
| spelling | doaj.art-62f3e5b1f9644beba8bd9fa5b5dd35672023-11-19T17:17:37ZengMDPI AGMedicina1010-660X1648-91442023-10-015910181310.3390/medicina59101813Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung CancerReem M. Abuhejail0Nourah Z. Alzoman1Ibrahim A. Darwish2Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia<i>Background and Objectives:</i> Ceritinib (CER) is a potent drug of the third-generation tyrosine kinase inhibitor class. CER has been approved for the treatment of patients with non-small-cell lung cancer (NSCLC) harboring the anaplastic lymphoma kinase (ALK) mutation gene. In the literature, there is no green and high-throughput analytical method for the quantitation of CER in its dosage form (Zykadia<sup>®</sup> capsules). This study describes, for the first time, the development and validation of two novel one-step and green microwell spectrophotometric methods (MW-SPMs) for the high-throughput quantitation of CER in Zykadia<sup>®</sup> capsules. <i>Materials and Methods:</i> These two methods were based on an <i>in microwell</i> formation of colored derivatives upon the reaction of CER with two different benzoquinone reagents via two different mechanisms. These reagents were <i>ortho</i>-benzoquinone (OBQ) and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), and their reactions proceeded via condensation and charge transfer reactions, respectively. The reactions were carried out in 96-well transparent plates, and the absorbances of the colored reaction products were measured with an absorbance microplate reader at 540 and 460 nm for reactions with OBQ and DDQ, respectively. The optimum conditions of reactions were established, their molar ratios were determined, and reaction mechanisms were postulated. Under the refined optimum reaction conditions, procedures of MW-SPMs were established and validated according to the guidelines of the International Council on Harmonization. <i>Results:</i> The limits of quantitation were 6.5 and 10.2 µg/well for methods involving reactions with OBQ and DDQ, respectively. Both methods were applied with great reliability to the determination of CER content in Zykadia<sup>®</sup> capsules and their drug uniformity. Greenness of the MW-SPMs was evaluated using three different metric tools, and the results proved that the two methods fulfil the requirements of green analytical approaches. In addition, the simultaneous handling of a large number of samples with microvolumes in the proposed methods gave them the advantage of a high-throughput analysis. <i>Conclusions</i>: The two methods are valuable tools for rapid routine application in pharmaceutical quality control units for the quantitation of CER.https://www.mdpi.com/1648-9144/59/10/1813ceritinibmicrowell analysisspectrophotometrygreen analytical approachhigh-throughput analysis |
| spellingShingle | Reem M. Abuhejail Nourah Z. Alzoman Ibrahim A. Darwish Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer Medicina ceritinib microwell analysis spectrophotometry green analytical approach high-throughput analysis |
| title | Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer |
| title_full | Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer |
| title_fullStr | Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer |
| title_full_unstemmed | Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer |
| title_short | Development of Two Novel One-Step and Green Microwell Spectrophotometric Methods for High-Throughput Determination of Ceritinib, a Potent Drug for Treatment of Anaplastic Lymphoma Kinase-Positive Non-Small-Cell Lung Cancer |
| title_sort | development of two novel one step and green microwell spectrophotometric methods for high throughput determination of ceritinib a potent drug for treatment of anaplastic lymphoma kinase positive non small cell lung cancer |
| topic | ceritinib microwell analysis spectrophotometry green analytical approach high-throughput analysis |
| url | https://www.mdpi.com/1648-9144/59/10/1813 |
| work_keys_str_mv | AT reemmabuhejail developmentoftwonovelonestepandgreenmicrowellspectrophotometricmethodsforhighthroughputdeterminationofceritinibapotentdrugfortreatmentofanaplasticlymphomakinasepositivenonsmallcelllungcancer AT nourahzalzoman developmentoftwonovelonestepandgreenmicrowellspectrophotometricmethodsforhighthroughputdeterminationofceritinibapotentdrugfortreatmentofanaplasticlymphomakinasepositivenonsmallcelllungcancer AT ibrahimadarwish developmentoftwonovelonestepandgreenmicrowellspectrophotometricmethodsforhighthroughputdeterminationofceritinibapotentdrugfortreatmentofanaplasticlymphomakinasepositivenonsmallcelllungcancer |