A simple and rapid HPLC-MS/MS method for therapeutic drug monitoring of amikacin in dried matrix spots
•A high-throughput method of amikacin in dried matrix spots by HPLC-MS/MS for therapeutic drug monitoring was established.•A stable isotope D5-amikacin internal standard was used instead of structure analogs to correct matrix effects in this method.•An excellent agreement of amikacin concentration i...
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Published in | Journal of chromatography. B, Analytical technologies in the biomedical and life sciences Vol. 1220; p. 123592 |
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Main Authors | , , , , , , , , , , |
Format | Journal Article |
Language | English |
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Elsevier B.V
01.04.2023
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Abstract | •A high-throughput method of amikacin in dried matrix spots by HPLC-MS/MS for therapeutic drug monitoring was established.•A stable isotope D5-amikacin internal standard was used instead of structure analogs to correct matrix effects in this method.•An excellent agreement of amikacin concentration in patients’ samples was shown in DSS and serum methods.•DMS provides convenient choices for amikacin TDM.
Individualized treatment of amikacin under the guidance of therapeutic drug monitoring (TDM) is important to reduce the occurrence of toxicity and improve clinical efficacy. In the present study, we developed and validated a simple and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine the concentration of amikacin in dried matrix spots (DMS) which the matrix is serum. DMS samples were obtained by spotting volumetric blood onto Whatman 903® cards. Samples were punched into 3 mm diameter discs and extracted with 0.2 % formic acid in water. The HILIC column (2.1 mm × 100 mm, 3.0 µm) under gradient elution was applied, and the analysis time was 3 min per injection. The mass spectrometry transitions were m/z 586.3 → 163.0 for amikacin and m/z 591.4 → 163.1 for D5-amikacin. Full validation was conducted for DMS method, and the method was applied for the amikacin TDM and compared with serum method. The linearity was ranged from 0.5 to 100 mg/L. Both within-run and between-run accuracy and precision of DMS ranged from 91.8 % to 109.6 % and 3.6 % to 14.2 %, respectively. The matrix effect was 100.5 %–106.5 % of DMS method. Amikacin remained stable in DMS for at least 6 days at room temperature, 16 days at 4 °C, 86 days at −20 °C and −70 °C. A good agreement between the DMS method and serum method has been shown in Bland-Altman plots and Passing-Bablok regression. All of the results demonstrated that the DMS methods can be a favorable replacement for amikacin TDM. |
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AbstractList | Individualized treatment of amikacin under the guidance of therapeutic drug monitoring (TDM) is important to reduce the occurrence of toxicity and improve clinical efficacy. In the present study, we developed and validated a simple and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine the concentration of amikacin in dried matrix spots (DMS) which the matrix is serum. DMS samples were obtained by spotting volumetric blood onto Whatman 903® cards. Samples were punched into 3 mm diameter discs and extracted with 0.2 % formic acid in water. The HILIC column (2.1 mm × 100 mm, 3.0 µm) under gradient elution was applied, and the analysis time was 3 min per injection. The mass spectrometry transitions were m/z 586.3 → 163.0 for amikacin and m/z 591.4 → 163.1 for D5-amikacin. Full validation was conducted for DMS method, and the method was applied for the amikacin TDM and compared with serum method. The linearity was ranged from 0.5 to 100 mg/L. Both within-run and between-run accuracy and precision of DMS ranged from 91.8 % to 109.6 % and 3.6 % to 14.2 %, respectively. The matrix effect was 100.5 %-106.5 % of DMS method. Amikacin remained stable in DMS for at least 6 days at room temperature, 16 days at 4 °C, 86 days at -20 °C and -70 °C. A good agreement between the DMS method and serum method has been shown in Bland-Altman plots and Passing-Bablok regression. All of the results demonstrated that the DMS methods can be a favorable replacement for amikacin TDM. •A high-throughput method of amikacin in dried matrix spots by HPLC-MS/MS for therapeutic drug monitoring was established.•A stable isotope D5-amikacin internal standard was used instead of structure analogs to correct matrix effects in this method.•An excellent agreement of amikacin concentration in patients’ samples was shown in DSS and serum methods.•DMS provides convenient choices for amikacin TDM. Individualized treatment of amikacin under the guidance of therapeutic drug monitoring (TDM) is important to reduce the occurrence of toxicity and improve clinical efficacy. In the present study, we developed and validated a simple and high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine the concentration of amikacin in dried matrix spots (DMS) which the matrix is serum. DMS samples were obtained by spotting volumetric blood onto Whatman 903® cards. Samples were punched into 3 mm diameter discs and extracted with 0.2 % formic acid in water. The HILIC column (2.1 mm × 100 mm, 3.0 µm) under gradient elution was applied, and the analysis time was 3 min per injection. The mass spectrometry transitions were m/z 586.3 → 163.0 for amikacin and m/z 591.4 → 163.1 for D5-amikacin. Full validation was conducted for DMS method, and the method was applied for the amikacin TDM and compared with serum method. The linearity was ranged from 0.5 to 100 mg/L. Both within-run and between-run accuracy and precision of DMS ranged from 91.8 % to 109.6 % and 3.6 % to 14.2 %, respectively. The matrix effect was 100.5 %–106.5 % of DMS method. Amikacin remained stable in DMS for at least 6 days at room temperature, 16 days at 4 °C, 86 days at −20 °C and −70 °C. A good agreement between the DMS method and serum method has been shown in Bland-Altman plots and Passing-Bablok regression. All of the results demonstrated that the DMS methods can be a favorable replacement for amikacin TDM. |
ArticleNumber | 123592 |
Author | Huang, Xiaolan Zhang, Jing Wang, Yu Chen, Mengting Wu, Hailan Fan, Yaxin Liu, Xiaofen Chen, Yan Li, Yi Guo, Beining Li, Xin |
Author_xml | – sequence: 1 givenname: Yan surname: Chen fullname: Chen, Yan – sequence: 2 givenname: Yu surname: Wang fullname: Wang, Yu – sequence: 3 givenname: Beining surname: Guo fullname: Guo, Beining – sequence: 4 givenname: Yaxin surname: Fan fullname: Fan, Yaxin – sequence: 5 givenname: Hailan surname: Wu fullname: Wu, Hailan – sequence: 6 givenname: Xin surname: Li fullname: Li, Xin – sequence: 7 givenname: Yi surname: Li fullname: Li, Yi – sequence: 8 givenname: Xiaolan surname: Huang fullname: Huang, Xiaolan – sequence: 9 givenname: Mengting surname: Chen fullname: Chen, Mengting – sequence: 10 givenname: Xiaofen surname: Liu fullname: Liu, Xiaofen email: liuxiaofen227@163.com – sequence: 11 givenname: Jing surname: Zhang fullname: Zhang, Jing email: zhangj_fudan@aliyun.com |
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Snippet | •A high-throughput method of amikacin in dried matrix spots by HPLC-MS/MS for therapeutic drug monitoring was established.•A stable isotope D5-amikacin... Individualized treatment of amikacin under the guidance of therapeutic drug monitoring (TDM) is important to reduce the occurrence of toxicity and improve... |
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SubjectTerms | Amikacin Chromatography, High Pressure Liquid - methods Chromatography, Liquid - methods Dried Blood Spot Testing - methods Dried matrix spot Drug Monitoring - methods HPLC-MS/MS Reproducibility of Results Serum Tandem Mass Spectrometry - methods Therapeutic drug monitoring |
Title | A simple and rapid HPLC-MS/MS method for therapeutic drug monitoring of amikacin in dried matrix spots |
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