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A simple, rapid, and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous quantitation of PA-824 and moxifloxacin in rat plasma using carbamazepine as an internal standard (IS). The sample preparation involved a one-step protein precipitation method with methanol. The separation was performed on Inertsil® ODS3 C18 column (150 mm × 4.6 mm, 5 μm) and maintained at 30 °C. The mobile phase consisted of 0.1% formic acid in acetonitrile–water (90:10 v/v) with fast isocratic elution at a flow rate of 0.6 mL/min and a run time of 10 min. A mass spectrometer was run in the positive ion electrospray ionization (ESI) mode using multiple reaction monitoring (MRM) to monitor the mass transitions. The MRM transitions were chosen to be m/z 360.1 → m/z 175.0 for PA-824, m/z 402.0 → m/z 383.9 for moxifloxacin, and m/z 237.1 → m/z 194.0 for IS. The method was fully validated in terms of selectivity, linearity, accuracy, precision, matrix effect, recovery, and stability, respectively. The method was successfully applied to drug–drug interaction (DDI) study of PA-824 and moxifloxacin in rats. The results show that the main pharmacokinetic parameters of PA-824, namely, T max, t 1/2, and AUC(0–t), increased more in the PA-824 and moxifloxacin group than in the PA-824 group. However, there were little changes in the main pharmacokinetic parameters of moxifloxacin from single and combined groups.

Open access
Acta Chromatographica
Authors:
Hao-ran Dai
,
Ya-hui Hu
,
Jia-yi Long
,
Ying Xia
,
Hong-li Guo
,
Jing Xu
,
Xuan-sheng Ding
,
Jing Chen
,
Xiao-peng Lu
, and
Feng Chen

Abstract

Perampanel (PER) is the first clinically available selective antagonist of α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor approved globally for the treatment of epilepsy. Studies have recently underlined the significant association between dose-exposure-effect-adverse events of PER in patients with epilepsy, so the therapeutic drug monitoring (TDM) of PER is critical in clinical practices, especially for pediatric patients with drug-resistant epilepsy. Due to several limits in previous published analytical methods, herein, we describe the development and validation of a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method for monitoring PER in human plasma samples. Protein precipitation method by acetonitrile containing PER-d5 as internal standard was applied for the sample clean-up. Formic acid (FA, 0.2 mM) in both aqueous water and acetonitrile were used as the mobile phases and the analyte was separated by an isocratic elution. Qualification and quantification were performed under positive electrospray ionization (ESI) mode using the m/z 350.3 → 219.1 and 355.3 → 220.0 ions pairs transitions for PER and PER-d5, respectively. Potential co-medicated anti-seizure medications (ASMs) have no interference to the analysis. Calibration curves were linear in the concentration range of 1.00–2,000 ng mL−1 for PER. The intra- and inter-batch precision, accuracy, recovery, dilution integrity, and stability of the method were all within the acceptable criteria and no matrix effect or carryover was found. This method was then successfully implemented on the TDM of PER in Chinese children with drug-resistant epilepsy. We firstly confirmed the apparent inter- and intra-individual PER concentration variabilities and potential drug-drug interactions between PER and several concomitant ASMs occurred in Chinese pediatric patients, which were also in line with previous studies in patients of other race.

Open access
Acta Chromatographica
Authors:
Chen Cheng
,
Nie Cun-Xi
,
Liang Jing
,
Wang Yong-Qiang
,
Liu Yan-Feng
,
Ge Wen-Xia
, and
Zhang Wen-Ju

A validated high-performance liquid chromatography (HPLC) method has been developed to analyze the (±)-gossypol in the selection of strains of Candida tropicalis culture. Since gossypol was easily degraded and oxidized, the addition of antioxidant NADPH-Na4 and acetone extraction was chosen to prevent gossypol degradation and gradient elution assay was applied to obtain gossypol resolution. Concentrations of gossypol in C. tropicalis ZD-3 culture 20 μg/mL were determined, and concentration–time profiles were observed. Linearity of the gossypol standard curve by HPLC area method was ranged from 0.1 to 20 μg/mL with Y = 26.954 × X − 29.547, R 2 = 0.9991, and n = 3, with limit of detection (LOD) of 50 ng/mL and lower limit of quantification (LLOQ) of 500 ng/mL. The recovery rate is dose-dependent and ranged from 85.3% to 103.5%. It is a rapid and reliable HPLC method for gossypol quantization in microorganism culture which could be applied in solid fermentation in the feed industry.

Open access
Journal of Behavioral Addictions
Authors:
Cheng Qin
,
Shuang Feng
,
Yuwen Chen
,
Xiaoyuan Liao
,
Xiaotong Cheng
,
Mingyuan Tian
,
Xinyi Zhou
,
Juan Deng
,
Yanjie Peng
,
Ke Gong
,
Kezhi Liu
,
Jing Chen
, and
Wei Lei

Abstract

Background and aims

The Pavlovian-to-instrumental transfer (PIT) effect is a phenomenon that Pavlovian conditioned cues that could influence one's instrumental behavior. In several substance and behavioral addictions, such as tobacco use disorder and gambling disorder, addiction-related cues could promote independently trained instrumental drug-seeking/drug-taking behaviors, indicating a specific PIT effect. However, it is unclear whether Internet gaming disorder (IGD) would show a similar change in PIT effects as other addictions. The study aimed to explore the specific PIT effects in IGD.

Methods

We administrated a PIT task to individuals with IGD (n = 40) and matched health controls (HCs, n = 50), and compared the magnitude of specific PIT effects between the two groups. The severity of the IGD symptoms was assessed by the Chinese version 9-item Internet Gaming Disorder Scale (IGDS) and the Internet Addiction Test (IAT).

Results

We found that: (1) related to the HCs group, the IGD group showed enhanced specific PITgame effects, where gaming-related cues lead to an increased choice rate of gaming-related responses; (2) in the IGD group, the magnitude of specific PITgame effects were positively correlated with IAT scores (rho = 0.39, p = 0.014).

Discussion and Conclusions

Individuals with IGD showed enhanced specific PIT effects related to HCs, which were associated with the severity of addictive symptoms. Our results highlighted the incentive salience of gaming-related cues in IGD.

Open access
Journal of Behavioral Addictions
Authors:
Ji-Bin Li
,
Anise M.S. Wu
,
Li-Fen Feng
,
Yang Deng
,
Jing-Hua Li
,
Yu-Xia Chen
,
Jin-Chen Mai
,
Phoenix K.H. Mo
, and
Joseph T.F. Lau

Abstract

Background and aims

Problematic online social networking use is prevalent among adolescents, but consensus about the instruments and their optimal cut-off points is lacking. This study derived an optimal cut-off point for the validated Online Social Networking Addiction (OSNA) scale to identify probable OSNA cases among Chinese adolescents.

Methods

A survey recruited 4,951 adolescent online social networking users. Latent profile analysis (LPA) and receiver operating characteristic curve (ROC) analyses were applied to the validated 8-item OSNA scale to determine its optimal cut-off point.

Results

The 3-class model was selected by multiple criteria, and validated in a randomly split-half subsample. Accordingly, participants were categorized into the low risk (36.4%), average risk (50.4%), and high risk (13.2%) groups. The highest risk group was regarded as “cases” and the rest as “non-cases”, serving as the reference standard in ROC analysis, which identified an optimal cut-off point of 23 (sensitivity: 97.2%, specificity: 95.2%). The cut-off point was used to classify participants into positive (probable case: 17:0%) and negative groups according to their OSNA scores. The positive group (probable cases) reported significantly longer duration and higher intensity of online social networking use, and higher prevalence of Internet addiction than the negative group.

Conclusions

The classification strategy and results are potentially useful for future research that measure problematic online social networking use and its impact on health among adolescents. The approach can facilitate research that requires cut-off points of screening tools but gold standards are unavailable.

Open access