Wyniki wyszukiwania - BazTech

1

LC-MS/MS method assay for simultaneous determination of the pretomanid and pyrazinamide in rat plasma by LC-MS/MS: Assessment of pharmacokinetic drug-drug interaction study

Huang Tao, Wang Li, Wang Fang, Shen Xin, Wang Libin

Acta Chromatographica

|

2024

|

Vol. 36, no. 1

7--13

EN

In the present study, an LC-MS/MS method allowing to quantify pretomanid and pyrazinamide simultaneously in rat plasma was developed. Chromatographic separation was achieved on an Agilent Eclipse plus C18 column (100 mm × 2.1 mm, 3.5 μm; Agilent, USA) and maintained at 30 °C. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 360.1 → m/z 175.1 for pretomanid, m/z 124.1 → m/z 81.0 for pyrazinamide, m/z 172.1 → m/z 128.1 for metronidazole (IS). The calibration curves showed good linear relationships over the concentration range of 50–7,500 ng mL⁻¹ for pretomanid and 500–75,000 ng mL⁻¹ for pyrazinamide. The precision and accuracy were below 15% and within ±15% of the nominal concentrations, respectively. The selectivity, recovery and matrix effect of this method were all within acceptable limits of bioanalytics. The method was applied to the analysis of plasma samples from pharmacokinetic studies in rats. The results show that the main pharmacokinetic parameters of pyrazinamide, namely, T max , t1/2, and AUC(0–t), decreased in the combined group than in the alone group.

2

UHPLC–Q/Orbitrap/MS/MS fingerprinting of Bai-Hu-Jia-Ren-Shen-Tang Decoction and evaluation of its antioxidant activity in streptozotocin-induced diabetic rats

Wang Libin, Shen Xin, Wang Fang, Xu Xiaohui

Acta Chromatographica

|

2023

|

Vol. 35, no. 4

293--301

EN

Bai-Hu-Jia-Ren-Shen-Tang Decoction (BHJRSTD) is one of the oldest classic Chinese medicine prescriptions which used in the field of treatment of diabetes. However, to the best of our knowledge, the ingredients of this prescription have not been identified, and there are very few studies on the anti-diabetic mechanism of this prescription. Therefore, BHJRSTD was detected and identified by ultra-high-performance liquid chromatography coupled with Quadrupole-Exactive Focus Orbitrap MS (UHPLC–Q/Orbitrap/MS/MS). We identified 74 compounds, including flavonoids, alkaloids, chalcones, xanthones, phenols, phenylpropanoids, terpenes, triterpenes, amino acid derivatives, etc. Then, Sprague Dawley rats were fed with a high-fat and high-sugar diet for two months and injected with streptozotocin (STZ) to induce type 2 diabetes (T2DM). The diabetic rats were randomized to given metformin (200 mg kg⁻¹•d⁻¹, n = 15), BHJRSTD extracts (40 g kg⁻¹•d⁻¹) and BHJRSTD extracts (10 g kg⁻¹•d⁻¹) by gavage for 8 weeks. The results confirmed that BHJRSTD significantly decreased the level of MDA and increased levels of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), it shows that the prescription has significant antioxidant activity in the treatment of T2DM.

3

Simultaneous determination of rivaroxaban and sitagliptin in rat plasma by LC–MS/MS and its application to pharmacokinetic drug-drug interaction study

Wang Libin, Shang Kun, Zhang Xiaorui, Zhang Xinying, Feng Tian, Xu Xiaohui, Wang Fang

Acta Chromatographica

|

2022

|

Vol. 34, no. 4

430--436

EN

A sensitive and accurate LC-MS/MS method was developed and validated for the simultaneous quantification of rivaroxaban (RIV) and sitagliptin (SIT) in rat plasma using apixaban as internal standard (IS). An Agilent Eclipse plus C18 column (2.1 × 100 mm, 3.5 µm, Agilent) was used for chromatographic separation with isocratic elution. Multiple reaction monitoring (MRM) using positive-ion ESI mode to monitor ion transitions of m/z 436.8→144.9 for RIV, m/z 407.7→173.8 for SIT, m/z 459.8→442.8 for IS. The procedure of method validation included selectivity, linearity, precision, accuracy, matrix effect, extraction recovery and stability were conducted according to the guidelines of EMA and FDA. The results indicated that no obvious drug-drug interactions occurred might be owing to their differences in metabolic pathways.

4

Study on the drug–drug interaction of antituberculosis drugs — PA-824 and moxifloxacin based on pharmacokinetics in rats by LC–MS/MS

Jing Juan, Jia Yuting, Feng Tian, Xie Tian, Li Zhoupeng, Hao Yong, Wang Libin

Acta Chromatographica

|

2019

|

Vol. 31, no. 3

206--210

EN

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, Tmax, t1/2, 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.

5

Study on pharmacokinetics, tissue distribution, and excretion of phloretin and its prodrug 2′,4′,6′,4-Tetra-O-acetylphloretin in rats using LC–MS/MS

Wang Libin, Li Xi, Mi Le, Shen Xin, Feng Tian, Liu Xueying, Wang Qingwei

Acta Chromatographica

|

2019

|

Vol. 31, no. 1

63--70

EN

2′,4′,6′,4-Tetra-O-acetylphloretin (TAPHL) is a prodrug of phloretin (PHL) in which the OH groups are protected by acetylation. A validated liquid chromatography–tandem mass spectrometry (LC–MS/MS) method for the determination of PHL in rat biological matrices was developed and applied to investigate and compare the pharmacokinetics, tissue distribution, and excretion of PHL and TAPHL in rats following a single oral administration. The method was validated for accuracy, precision, linearity, range, selectivity, lower limit of quantification (LLOQ), recovery, and matrix effect. All validation parameters met the acceptance criteria according to regulatory guidelines. The mean pharmacokinetic parameters of tmax, Cmax, AUC(0 − t), CL/F, and t1/2 were observed after oral administration in rats. The data showed that PHL was absorbed and eliminated rapidly from plasma after oral administration. The pharmacokinetic properties are improved, such as the tmax has been prolonged and the area under the curve (AUC) has been enhanced after oral administration of TAPHL to rats. Tissue distribution results indicated that PHL could be rapidly and widely distributed into tissues but could not effectively cross the blood–brain barrier in rats. After oral administration of TAPHL to rats, its tissue distribution to rats was similar as that after oral administration of equimolar PHL. In addition, higher recoveries of PHL following administration of TAPHL indicated that TAPHL might reduce the excretion of PHL from the body by reducing the first pass effect.