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Simultaneous determination of eight antiepileptic drugs and two metabolites in human plasma by liquid chromatography/tandem mass spectrometry

Yu Hengyi, Ren Xiuhua, Liu Lu, Xiang Dong, Li Xiping, Li Juan, Liu Dong, Gong Xuepeng

Acta Chromatographica

2023

Vol. 35, no. 2

161--169

Epilepsy is one of the most prevalent neurological conditions and antiepileptic drugs are the mainstay of epilepsy treatment. High variation in pharmacokinetic profiles of several antiepileptic drugs highlights the importance of therapeutic drug monitoring to estimate pharmacokinetic properties and consequently individualize drug posology. In this work, a simple, rapid and robust liquid chromatography-tandem mass spectrometry method was developed for simultaneous quantification of carbamazepine and its metabolite carbamazepine-10,11-epoxide, gabapentin, levetiracetam, lamotrigine, oxcarbazepine and its metabolite mono-hydroxy-derivative metabolite, phenytoin, topiramate, and valproic acid in human plasma for therapeutic drug monitoring. d6-Levetiracetam, d4-gabapentin and d6-valproic acid were used as internal standards. After addition of internal standards along with two-step protein precipitation and dilution sample preparation, plasma samples were analyzed on a C18 column using a gradient elution in 5 min without interference. The calibration curves were linear over a 100-fold concentration range, with determination coefficients (r2) greater than 0.99 for all analytes. The limit of quantification was 0.5 μg mL⁻¹ (0.1 μg mL⁻¹ for oxcarbazepine, 2 μg mL⁻¹ for levetiracetam, and 10 μg mL⁻¹ for valproic acid) with precision and accuracy ranging from 3% to 9% and from 94% to 112%, respectively. Intra- and inter-day precision and accuracy values were within 15% at low, medium and high quality control levels. No significant matrix effect was observed in the normal, hemolyzed, lipemic, and hyperbilirubin blood samples. This method was successfully used in the identification and quantitation of antiepileptic drugs in patients undergoing mono- or polytherapy for epilepsy.

Prediction of ship motions via a three-dimensional time-domain method following a quad-tree adaptive mesh technique

Zhang Teng, Ren Junsheng, Liu Lu

Polish Maritime Research

2020

nr 1

29--38

A three-dimensional (3D) time-domain method is developed to predict ship motions in waves. To evaluate the Froude- Krylov (F-K) forces and hydrostatic forces under the instantaneous incident wave profile, an adaptive mesh technique based on a quad-tree subdivision is adopted to generate instantaneous wet meshes for ship. For quadrilateral panels under both mean free surface and instantaneous incident wave profiles, Froude-Krylov forces and hydrostatic forces are computed by analytical exact pressure integration expressions, allowing for considerably coarse meshes without loss of accuracy. And for quadrilateral panels interacting with the wave profile, F-K and hydrostatic forces are evaluated following a quad-tree subdivision. The transient free surface Green function (TFSGF) is essential to evaluate radiation and diffraction forces based on linear theory. To reduce the numerical error due to unclear partition, a precise integration method is applied to solve the TFSGF in the partition computation time domain. Computations are carried out for a Wigley hull form and S175 container ship, and the results show good agreement with both experimental results and published results.