A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma
A sensitive, rapid, simple and economical ultra-performance liquid chromatographyâtandem mass spectrometric method (UPLCâMS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid ex...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2017-12-01
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| Series: | Journal of Pharmaceutical Analysis |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2095177917300977 |
| _version_ | 1819088829207805952 |
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| author | Jing Zeng Hua lin Cai Zhi ping Jiang Qing Wang Yan Zhu Ping Xu Xie lan Zhao |
| author_facet | Jing Zeng Hua lin Cai Zhi ping Jiang Qing Wang Yan Zhu Ping Xu Xie lan Zhao |
| author_sort | Jing Zeng |
| collection | DOAJ |
| description | A sensitive, rapid, simple and economical ultra-performance liquid chromatographyâtandem mass spectrometric method (UPLCâMS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate) and B (organic phase: acetonitrile) (A:B=40:60, v/v). The flow rate was 0.25Â mL/min and the total run time was 6Â min. The multiple reaction monitoring (MRM) transitions, m/z 494.5â394.5 for imatinib, 488.7â401.5 for dasatinib, 530.7â289.5 for nilotinib and 528.5â403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6â5250.0Â ng/mL for imatinib, 2.0â490.0Â ng/mL for dasatinib, and 2.4â4700.0Â ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLCâMS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 â1889T>C or SLCO1B3 699G>A genotypes (P>0.05). This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors (TKIs). Keywords: UPLCâMS/MS, Imatinib, Dasatinib, Nilotinib, Polymorphism |
| first_indexed | 2024-12-21T21:58:15Z |
| format | Article |
| id | doaj.art-1d00fdcb2ba94d83937378b0587d2719 |
| institution | Directory Open Access Journal |
| issn | 2095-1779 |
| language | English |
| last_indexed | 2024-12-21T21:58:15Z |
| publishDate | 2017-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Pharmaceutical Analysis |
| spelling | doaj.art-1d00fdcb2ba94d83937378b0587d27192022-12-21T18:48:55ZengElsevierJournal of Pharmaceutical Analysis2095-17792017-12-0176374380A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasmaJing Zeng0Hua lin Cai1Zhi ping Jiang2Qing Wang3Yan Zhu4Ping Xu5Xie lan Zhao6Department of Pharmacy, the Second Xiangya Hospital, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Pharmacy, the Second Xiangya Hospital, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Hematology, Xiangya Hospital, Central South University, NO87, Xiangya Road, Changsha, Hunan 410008, ChinaDepartment of Pharmacy, the Second Xiangya Hospital, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Pharmacy, the Second Xiangya Hospital, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, ChinaDepartment of Pharmacy, the Second Xiangya Hospital, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, China; Institute of Clinical Pharmacy, Central South University, NO139, Renmin Road, Changsha, Hunan 410011, China; Corresponding author at: Department of Pharmacy, the Second Xiangya Hospital, Central South University, NO139, Renmin Road, Changsha, Hunan, China.Department of Hematology, Xiangya Hospital, Central South University, NO87, Xiangya Road, Changsha, Hunan 410008, ChinaA sensitive, rapid, simple and economical ultra-performance liquid chromatographyâtandem mass spectrometric method (UPLCâMS/MS) was developed and validated for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma using gliquidone as internal standard (IS). Liquid-liquid extraction method with ethyl acetate was used for sample pre-treatment. The separation was performed on an Xtimate Phenyl column using isocratic mobile phase consisting of A (aqueous phase: 0.15% formic acid and 0.05% ammonium acetate) and B (organic phase: acetonitrile) (A:B=40:60, v/v). The flow rate was 0.25Â mL/min and the total run time was 6Â min. The multiple reaction monitoring (MRM) transitions, m/z 494.5â394.5 for imatinib, 488.7â401.5 for dasatinib, 530.7â289.5 for nilotinib and 528.5â403.4 for IS, were chosen to achieve high selectivity in the simultaneous analyses. The method exhibited great improvement in sensitivity and good linearity over the concentration range of 2.6â5250.0Â ng/mL for imatinib, 2.0â490.0Â ng/mL for dasatinib, and 2.4â4700.0Â ng/mL for nilotinib. The method showed acceptable results on sensitivity, specificity, recovery, precision, accuracy and stability tests. This UPLCâMS/MS assay was successfully used for human plasma samples analysis and no significant differences were found in imatinib steady-state trough concentrations among the SLC22A5 â1889T>C or SLCO1B3 699G>A genotypes (P>0.05). This validated method can provide support for clinical therapeutic drug monitoring and pharmacokinetic investigations of these three tyrosine kinase inhibitors (TKIs). Keywords: UPLCâMS/MS, Imatinib, Dasatinib, Nilotinib, Polymorphismhttp://www.sciencedirect.com/science/article/pii/S2095177917300977 |
| spellingShingle | Jing Zeng Hua lin Cai Zhi ping Jiang Qing Wang Yan Zhu Ping Xu Xie lan Zhao A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma Journal of Pharmaceutical Analysis |
| title | A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma |
| title_full | A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma |
| title_fullStr | A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma |
| title_full_unstemmed | A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma |
| title_short | A validated UPLCâMS/MS method for simultaneous determination of imatinib, dasatinib and nilotinib in human plasma |
| title_sort | validated uplcams ms method for simultaneous determination of imatinib dasatinib and nilotinib in human plasma |
| url | http://www.sciencedirect.com/science/article/pii/S2095177917300977 |
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