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Development of a useful single-reference HPLC method for therapeutic drug monitoring of phenytoin and carbamazepine in human plasma

  • Special Issue: Original Paper
  • Frontiers of Separation Analysis
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Abstract

A single reference high-performance liquid chromatographic (SR-HPLC) method was developed and validated for the therapeutic drug monitoring (TDM) of phenytoin (PHT) and carbamazepine (CBZ) in plasma from patients. The analytical parameters evaluated were linearity, limit of quantification (LOQ), selectivity, accuracy, and stability according to the US Food and Drug Administration (FDA) guideline. The developed method shows good linearity (r2 > 0.999; LOQ—50 µg/mL), and LOQ values were 1.56 µg/mL for PHT and 0.40 µg/mL for CBZ at 254 nm. For the development of SR-HPLC method, we evaluated to improve the detection wavelength, stirred retention time, and stability for SR, and selected 5-(p-methylphenyl)-5-phenylhydantoin for PHT (relative molar sensitivity, RMS = 0.848) and 10-methoxyiminostilbene for CBZ (RMS = 0.263). The established differential definite quantities of PHT and CBZ in plasma samples were similar using the RMS and absolute calibration methods based on RSD < 5.10%. A preliminary application was performed using chemiluminescent immunoassay and SR-HPLC method, in which the detectable values of the correlation coefficient and the slope of the intercept were PHT: 0.964 and 0.992647, and CBZ: 0.969 and 1.072089, respectively. Based on these results, we propose that the SR-HPLC method with RMS would be offered to the useful and accurate TDM of various medicines in plasma/serum samples.

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Data availability

On reasonable request, derived data supporting the findings of this study are available from the corresponding author after approval from the Ethical Committee of the Ritsumeikan University.

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Acknowledgements

We thank Dr. Miki Takahashi, Dr. Yuzo Nishizaki, Dr. Naoki Sugimoto, and Dr. Kyoko Sato from National Institute of Health Sciences, Japan for their technical assistance and SR advice.

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Authors and Affiliations

  1. Laboratory of Clinical and Analytical Chemistry, College of Pharmaceutical Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga, 525-8577, Japan

    Yuko Sakaguchi, Ryo Arima, Runa Maeda, Nobuhiro Ichikawa & Koichi Inoue

  2. Department of Pharmacy, Japanese Red Cross Kyoto Daiichi Hospital, 15-749 Honmachi, Higashiyama-Ku, Kyoto, Kyoto, 605-0981, Japan

    Takuji Obayashi, Akihide Masuda, Mari Funakoshi & Yumi Tsuchiya

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  1. Yuko Sakaguchi
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Correspondence to Yuko Sakaguchi.

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Sakaguchi, Y., Arima, R., Maeda, R. et al. Development of a useful single-reference HPLC method for therapeutic drug monitoring of phenytoin and carbamazepine in human plasma. ANAL. SCI. 39, 447–454 (2023). https://doi.org/10.1007/s44211-023-00266-z

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  • DOI: https://doi.org/10.1007/s44211-023-00266-z

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