Development and validation of a liquid chromatography‐tandem mass spectrometry method with triple‐stage fragmentation to determine levetiracetam in epileptic patient serum and its application in therapeutic drug monitoring

Ji, Zhengchao; Yin, Lei; Li, Yanyan; Yang, Xiao‐Quan; Lin, Lin; Liu, Lingling; Jiang, Yiguo; Huang, Jing

doi:10.1002/jssc.202100639

Cited by 5 publications

(5 citation statements)

References 26 publications

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“…Targeted metabolomics was performed as previously reported [ 28 , 29 ]. For sample preparation for quality control (QC) and isotope internal (IS) standards, nine metabolite standards and the IS were dissolved with 90% acetonitrile to a final concentration of 1 mg/mL.…”

Section: Methodsmentioning

confidence: 99%

LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells

et al. 2022

BMC Cancer

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Background IFN-γ has been traditionally recognized as an inflammatory cytokine that involves in inflammation and autoimmune diseases. Previously we have shown that sustained IFN-γ induced malignant transformation of bovine mammary epithelial cells (BMECs) via arginine depletion. However, the molecular mechanism underlying this is still unknown. Methods In this study, the amino acids contents in BMECs were quantified by a targeted metabolomics method. The acquisition of differentially expressed genes was mined from RNA-seq dataset and analyzed bioinformatically. Quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), western blotting, and immunohistochemistry (IHC) assay were performed to detect gene mRNA and protein expression levels. CCK-8 and would healing assays were used to detect cell proliferation and migration abilities, respectively. Cell cycle phase alternations were analyzed by flow cytometry. Results The targeted metabolomics analysis specifically discovered IFN-γ induced arginine depletion through accelerating arginine catabolism and inhibiting arginine anabolism in BMECs. Transcriptome analysis identified leucine aminopeptidase 3 (LAP3), which was regulated by p38 and ERK MAPKs, to downregulate arginine level through interfering with argininosuccinate synthetase (ASS1) as IFN-γ stimulated. Moreover, LAP3 also contributed to IFN-γ-induced malignant transformation of BMECs by upregulation of HDAC2 (histone deacetylase 2) expression and promotion of cell cycle proteins cyclin A1 and D1 expressions. Arginine supplementation did not affect LAP3 and HDAC2 expressions, but slowed down cell cycle process of malignant BMECs. In clinical samples of patients with breast cancer, LAP3 was confirmed to be upregulated, while ASS1 was downregulated compared with healthy control. Conclusions These results demonstrated that LAP3 mediated IFN-γ-induced arginine depletion to malignant transformation of BMECs. Our findings provide a potential therapeutic target for breast cancer both in humans and dairy cows.

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Section: Methodsmentioning

confidence: 99%

LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells

et al. 2022

BMC Cancer

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“…In addition, first-generation AEDs such as carbamazepine (CBZ), ethosuximide (ESM), phenobarbital (PHB), phenytoin (PHT), primidone (PRM), and valproic acid are still widely used in primary hospital of China or other developing countries. Thus, therapeutic drug monitoring (TDM) is still necessary for the clinical management of patients with epilepsy [13][14][15]. Several techniques are available for TDM of AEDs.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, only a limited number of the newer AEDs are quantifiable by the technique [5,18]. Chromatographybased methods, which can fulfill simultaneous separation, and accurate and sensitive determination of multiple compounds, have been widely implemented in the TDM of AEDs, such as GC coupled with flame ionization [19], electron capture [20], nitrogen-phosphorus [20] or MS detector [21], HPLC or UHPLC coupled with UV-visible (UV-VIS) [22], electrochemical [23], fluorescence [24] or mass spectrometry (MS) detector [13,25], and high-performance CE (HPCE) [26]. Among those methods, for its lower cost and higher applicability for most drugs, HPLC-UV is more suitable than the others for TDM of AEDs in most hospitals, especially primary hospitals in developing countries [18,[27][28][29].…”

Section: Introductionmentioning

confidence: 99%

Development and evaluation of a simple and easy high‐performance liquid chromatography–ultraviolet system simultaneously suitable for determination of 24 anti‐epileptic drugs in plasma

Zhao¹,

Lifan

You

et al. 2022

J of Separation Science

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We aim to establish a simple and easy high-performance liquid chromatography system coupled with an ultraviolet detector suitable for simultaneous determination of 24 antiepileptic drugs in human plasma. Optimized chromatographic separation was performed on a ZORBAX Eclipse Plus-C18 (4.6 × 150 mm 2 , 3.5 μm) column with acetonitrile and 5 mM potassium dihydrogen phosphate water solution as mobile phase. Note that, 24 antiepileptic drugs were divided into three groups and eluted with different gradient procedures, respectively. The column temperature was maintained at 35 • C and the detection wavelength was set at 210 nm. Plasma was processed with ethyl acetate or acetonitrile. The calibration curves of 24 antiepileptic drugs demonstrated good linearity within the test range (r > 0.996). The intra-and inter-batch precision and accuracy were all less than 15%, while extraction recoveries were in the range of 74.57-90.89% with the relative standard deviation values less than 15%. The validated methods have been successfully applied to determination of some antiepileptic drugs in rat or patient plasma. Those results indicated that the developed methods were simple and easy, and could be suitable for the determination of 24 antiepileptic drugs in plasma just by changing the gradient elution procedures of mobile phase.

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“…In addition, pharmacokinetic or pharmacodynamics interaction between AEDs and other drugs also is a non-negligible factor that influences drug concentration and therapeutic effect [7][8][9][10]. Therefore, it will be better if therapeutic drug monitoring (TDM) for the clinical management of epileptic patients with second-or third-generation AEDs is performed [11,12]. TDM has been defined as the measurement and clinical use of drug concentration to optimize the patient's outcome, thereby individualizing treatment [12].…”

Section: Introductionmentioning

confidence: 99%

A simple and easy non‐derivatization gas chromatography‐mass spectrometry method for simultaneous quantification of valproic acid, gabapentin, pregabalin, and vigabatrin in human plasma

Jin

You

Lifan

et al. 2022

J of Separation Science

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Immunoassays are currently not available in commercial kits for the quantification of valproic acid, vigabatrin, pregabalin, and gabapentin, which also cannot suffer the limitations of interferences of substances with similar structures. Chromatography is a good alternative to immunoassay. In this study, a simple and robust non-derivatization gas chromatography-mass spectrometry method for simultaneous determination of the above four drugs in human plasma was developed and validated for therapeutic drug monitoring purposes. This method employed benzoic acid as the internal standard with hydrochloric acid for plasma acidification and ACN for precipitate protein. The supernatant was directly injected into gas chromatography-mass spectrometry for analysis. Good linearity was obtained with linear correlation coefficients of the four analytes of 0.9988-0.9996. Extraction recoveries of valproic acid, vigabatrin, pregabalin, and gabapentin were respectively in the ranges of 91.3%-94.5%, 90.0%-90.9%, 90.0%-92.1%, and 88.0%-92.2% with the relative standard deviation values less than 12.6%. Intra-and inter-batch precision and accuracy, and stability assays were all acceptable. Taken together, the novel method developed in this study provided easy plasma pretreatment, good extraction yield, and high chromatographic resolution, which has been successfully validated through the quantification of valproic acid in the plasma of 46 patients with epilepsy.

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Development and validation of a liquid chromatography‐tandem mass spectrometry method with triple‐stage fragmentation to determine levetiracetam in epileptic patient serum and its application in therapeutic drug monitoring

Cited by 5 publications

References 26 publications

LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells

LAP3 contributes to IFN-γ-induced arginine depletion and malignant transformation of bovine mammary epithelial cells

Development and evaluation of a simple and easy high‐performance liquid chromatography–ultraviolet system simultaneously suitable for determination of 24 anti‐epileptic drugs in plasma

A simple and easy non‐derivatization gas chromatography‐mass spectrometry method for simultaneous quantification of valproic acid, gabapentin, pregabalin, and vigabatrin in human plasma

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