Therapeutic drug monitoring of free perampanel concentrations in practice: A practical analytical technique based on centrifugal ultrafiltration sample separation
Ying-Hua Ma,
Lei Dong,
Jia-Xuan Wu,
Shi-Yuan Hu,
Xiang-Fei Meng,
Yi-Le Zhao,
Kang Liu,
Dan-Ni Yan,
Su-Zhen Sun
Affiliations
Ying-Hua Ma
Department of Pharmacy, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China
Lei Dong
Department of Pharmacy, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China; College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China; Corresponding author. Department of Pharmacy, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China.
Jia-Xuan Wu
College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China
Shi-Yuan Hu
College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China
Xiang-Fei Meng
College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei, 050017, PR China
Yi-Le Zhao
Department of Pharmacy, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China
Kang Liu
Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China; The Key Laboratory of Pediatric Epilepsy and Neuropathy of Hebei Province, Shijiazhuang, PR China
Dan-Ni Yan
Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China; The Key Laboratory of Pediatric Epilepsy and Neuropathy of Hebei Province, Shijiazhuang, PR China
Su-Zhen Sun
Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China; The Key Laboratory of Pediatric Epilepsy and Neuropathy of Hebei Province, Shijiazhuang, PR China; Corresponding author. Department of Neurology, Children's Hospital of Hebei Province, Shijiazhuang, 050031, PR China.
Objectives: The centrifugal ultrafiltration–high-performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was established to determine the free perampanel (PER) concentration in children with epilepsy. Methods: Free PER concentration was obtained using centrifugal ultrafiltration devices. The internal standard was PER-D5. The method was investigated for selectivity, carryover, lower limit of quantification, calibration curve, accuracy, precision, matrix effects, recovery, and stability. The Spearman's correlation coefficient was used to evaluate the correlation between the free and total PER concentrations. A nonparametric test was used to estimate the effects of PER along with other antiepileptic drugs on the total and free PER concentrations. Results: The free PER concentration was positively correlated with the total PER concentration in the 57 plasma samples (r = 0.793 > 0, P < 0.001). Additionally, the free PER concentrations were significantly (P < 0.05) increased in valproic acid (VPA) co-therapy (9.87 ± 5.83) compared with non-VPA co-therapy (5.03 ± 4.57). Conclusions: The proposed method is efficient, sensitive, and suitable for detecting free PER concentrations in children with epilepsy. Simultaneously, the free PER concentration response to clinical outcomes in children with epilepsy was more clinically significant, particularly when combined with VPA.
