Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring
A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS<sup>3</sup>) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated...
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MDPI AG
2022-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/17/5670 |
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| author | Zhengchao Ji Tingting Li Xin Zhao Wei Ma Yanyan Li Jing Huang |
| author_facet | Zhengchao Ji Tingting Li Xin Zhao Wei Ma Yanyan Li Jing Huang |
| author_sort | Zhengchao Ji |
| collection | DOAJ |
| description | A sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS<sup>3</sup>) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, <i>v:v</i>) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS<sup>3</sup> method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing–Bablok regression coefficients and Bland–Altman plots showed that the developed LC–MS<sup>3</sup> method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS<sup>3</sup> method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study. |
| first_indexed | 2024-03-10T01:28:46Z |
| format | Article |
| id | doaj.art-77749e1e63464e468fb2080eff811e4b |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T01:28:46Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-77749e1e63464e468fb2080eff811e4b2023-11-23T13:46:07ZengMDPI AGMolecules1420-30492022-09-012717567010.3390/molecules27175670Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug MonitoringZhengchao Ji0Tingting Li1Xin Zhao2Wei Ma3Yanyan Li4Jing Huang5Department of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130021, ChinaVascular Surgery, General Surgery Center, The First Hospital of Jilin University, Jilin University, Changchun 130021, ChinaDepartment of Health Examination Center, The First Hospital of Jilin University, Jilin University, Changchun 130021, ChinaDepartment of Pharmacy, The First Hospital of Jilin University, Jilin University, Changchun 130021, ChinaDepartment of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130021, ChinaDepartment of Laboratory Medicine, The First Hospital of Jilin University, Jilin University, Changchun 130021, ChinaA sensitive and rapid bioanalytical method based on the LC-triple-stage fragmentation (LC-MS<sup>3</sup>) strategy on a hybrid triple quadrupole-linear ion trap mass spectrometer in combination with protein precipitation extraction for sample pretreatment has been developed and validated for the simultaneous determination of the antiepileptic drug oxcarbazepine (OXC) and its main active metabolite (MHD) in human serum. The separation was performed on a Waters XBridge BEH C18 column (2.5 µm, 2.1 × 50 mm) in isocratic elution with 0.1% formic acid in water and methanol (50:50, <i>v:v</i>) as the mobile phase. The run time for each sample was 2.0 min. The calibration curves ranging from 25 to 1600 ng/mL for OXC and from 0.5 to 32 μg/mL for MHD showed correlation coefficients (r) better than 0.99. All of the validation data, such as precision, accuracy and other parameters, fit the requirements of the current bioanalytical method validation guidelines. The LC-MS<sup>3</sup> method for quantitation of OXC and MHD was compared with the LC-MRM based method. Passing–Bablok regression coefficients and Bland–Altman plots showed that the developed LC–MS<sup>3</sup> method is a reliable method for quantitative analysis of OXC and MHD. The proposed LC-MS<sup>3</sup> method was successfully applied to determine the serum concentrations of OXC and MHD to support a clinical study.https://www.mdpi.com/1420-3049/27/17/5670oxcarbazepine10-hydroxycarbazepineLC-MS<sup>3</sup>validationtherapeutic drug monitoring |
| spellingShingle | Zhengchao Ji Tingting Li Xin Zhao Wei Ma Yanyan Li Jing Huang Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring Molecules oxcarbazepine 10-hydroxycarbazepine LC-MS<sup>3</sup> validation therapeutic drug monitoring |
| title | Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring |
| title_full | Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring |
| title_fullStr | Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring |
| title_full_unstemmed | Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring |
| title_short | Development and Validation of a Highly Sensitive and Rapid LC-MS<sup>3</sup> Strategy to Determine Oxcarbazepine and Its Active Metabolite in the Serum of Patients with Epilepsy and Its Application in Therapeutic Drug Monitoring |
| title_sort | development and validation of a highly sensitive and rapid lc ms sup 3 sup strategy to determine oxcarbazepine and its active metabolite in the serum of patients with epilepsy and its application in therapeutic drug monitoring |
| topic | oxcarbazepine 10-hydroxycarbazepine LC-MS<sup>3</sup> validation therapeutic drug monitoring |
| url | https://www.mdpi.com/1420-3049/27/17/5670 |
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