An UPLC–MS/MS method for the quantitation of vortioxetine in rat plasma: Application to a pharmacokinetic study

Gu, Er-min; Huang, Chengke; Liang, Bo; Yuan, Ling-jing; Lan, Tian; Hu, Guoxin; Zhou, Hongyu

doi:10.1016/j.jchromb.2015.05.010

Cited by 27 publications

(16 citation statements)

References 16 publications

(28 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Both methods utilize a gradient elution and the samples were prepared with protein precipitation (PPT). Compared with the previous published UHPLC‐MS/MS method for the detection of VOT in rat plasma , the run time in our method is 3.0 min, which is shorter than the reported method, and so our procedure has a time‐saving advantage. In addition, LLE is utilized for sample preparation in our method, as samples treated by LLE are cleaner than if treated by PPT, and thus, can protect columns and instruments.…”

Section: Resultsmentioning

confidence: 86%

Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry

Guan

Zou

Jia

et al. 2018

J of Separation Science

View full text Add to dashboard Cite

Vortioxetine is a multimodal antidepressant that has been recently utilized globally. Vortioxetine hemi‐hydrochloride is a novel salt that was previously reported in our research. However, the pharmacokinetics of this salt and the metabolites of Vortioxetine in vivo remain unknown. In this study, the pharmacokinetics of the Vortioxetine hemi‐hydrochloride salt is explored in rats through a newly developed ultra‐performance liquid chromatography with tandem mass spectrometry method. In addition, ultra‐performance liquid chromatography coupled with quadrupole time of flight mass spectrometry was used to identify the metabolites of Vortioxetine in vivo. The results demonstrate that after a single, 3 mg/kg oral dose, the maximum concentration for the Vortioxetine hemi‐hydrochloride salt is 14.63 ± 4.00 ng/mL, and is attained in 1.00∼4.00 h. The area under the plasma concentration‐time curve from time 0 to 24 h is 67.30 ± 23.78 ng·h·mL−1. Additionally, 29 metabolites were identified after the oral administration of 10 mg/kg, including 17 metabolites in the plasma, nine in the urine, and 12 in the feces. Eleven metabolites were novel. The major metabolic pathways include methylation, hydroxylation, oxidation, and glucuronidation. In conclusion, this study provides insight for further development of the Vortioxetine hemi‐hydrochloride salt.

show abstract

Section: Resultsmentioning

confidence: 86%

Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry

Guan

Zou

Jia

et al. 2018

J of Separation Science

View full text Add to dashboard Cite

show abstract

“…According to previous research, trifluoroacetic acid (Liu et al, 2016) and formic acid Gu et al, 2015;Huang et al, 2016) were used as mobile phase additives; therefore, ACN (30-50%) and water with trifluoroacetic acid, formic acid or acetic acid, at different concentrations (0.02-0.1%) were tested, but VOR eluted with the solvent front and with low efficiency and symmetry. In order to obtain a fast analysis, initial trials were started using a monolithic column: a Chromolith ® Performance RP 18 column (100 × 3 mm) was tested.…”

Section: Optimization Of Chromatographic Conditionsmentioning

confidence: 99%

“…2016) for determination of genotoxic impurity from the synthesis route. There are other methods for determination of VOR in biological samples, such as UPLC-MS methods for analysis in rat plasma (Gu et al, 2015;Huang et al, 2016), HPLC-DAD and HPLC-MS analysis in human serum and saliva (Wróblewski et al, 2017), and HPLC-MS and UPLC-MS methods for the quantification of VOR and its major human metabolite in human plasma (Kall, Rohde, & Jorgensen, 2015). To the authors' knowledge, there is no method for the determination of VOR in presence of its mayor DP.…”

Section: Introductionmentioning

confidence: 99%

Determination of vortioxetine and its degradation product in bulk and tablets, by LC‐DAD and MS/MS methods

Diego

Correa

Mennickent

et al. 2018

Biomedical Chromatography

View full text Add to dashboard Cite

Vortioxetine hydrobromide (VOR), is a novel antidepressant used for the treatment of major depressive disorder. It has a chemical structure susceptible to degradation, therefore it is important to have suitable analytical methods to determine VOR in presence of its main degradation products (DP), because if the compound degrades, this could result in diminution of the therapeutic activity and safety. A simple HPLC method with photodiode array detection was developed and validated for determination of VOR in bulk and tablets, in the presence of its major DP. The drug was subjected to oxidative, hydrolytic, and photolytic stress conditions, showing significant degradation under oxidation with the formation of one DP, which was identified by ESI-MS/MS. A C 18 column was used, with mobile phase consisting of acetonitrile and water with acetic acid and triethylamine in isocratic elution mode, with detection at 228 nm and 1.0 mL/min flow rate. The assay was linear in the 25-125 μg/mL concentration range. For precision, the RSD was <1.8%, the recovery was 100.0-101.6%, and the method demonstrated adequate selectivity. The method was successfully applied to quantify VOR in tablets. The results showed that the method is useful for routine analysis and for quality control purposes.

show abstract

“…In the paper, the 13 C-labeled analogs of the analytes were applied and MS detection was used. Gu et al described the ultra-performance liquid chromatography (UPLC) method for quantitation of vortioxetine in rat plasma on the C18 column with mobile phase containing 0.1% formic acid in water and acetonitrile with gradient elution [11]. The sample preparation in the above procedure relays on the protein precipitation.…”

Section: Introductionmentioning

confidence: 99%

“…For instance, oral fluid is gaining importance as a specimen in clinical and forensic toxicology for determination of many antidepressants or sedative drugs. This is also reflected in a significant increase in the interest in oral fluid drug analysis in recent years [13].…”

Section: Introductionmentioning

confidence: 99%

Determination of vortioxetine in human serum and saliva samples by HPLC–DAD and HPLC–MS

Wróblewski

Petruczynik

Buszewski

et al. 2017

Acta Chromatographica

View full text Add to dashboard Cite

Summary. Vortioxetine is a new drug against major depressive disorder with high affinity for a range of different serotonergic targets in the central nervous system. Therapeutic drug monitoring is an important tool for the clinical management of patients receiving a pharmacotherapy, particularly in psychiatry. For this reason, determination of drug concentration in biological fluids is important for a rational dosage of drugs. Rapid and reliable analytical assays are also required to detect and identify drugs of toxicological importance. For analysis of vortioxetine by high-performance liquid chromatography (HPLC), no procedures for its determination in saliva have been reported and there are only a few ones for its determination in serum. A sensitive and selective highperformance liquid chromatography with diode array detector (HPLC-DAD) or mass spectrometer (HPLC-MS) method was developed for the fast quantification of vortioxetine in human saliva and serum. The determination was performed on a Synergi Polar RP column in isocratic mode under the optimal mobile phase containing 70% methanol, 20% acetate buffer at pH 3.5, 10% double distilled water, and 0.025 M L −1 diethylamine.

show abstract

An UPLC–MS/MS method for the quantitation of vortioxetine in rat plasma: Application to a pharmacokinetic study

Cited by 27 publications

References 16 publications

Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry

Pharmacokinetic and metabolic studies of Vortioxetine in rats using ultra high performance liquid chromatography with tandem mass spectrometry

Determination of vortioxetine and its degradation product in bulk and tablets, by LC‐DAD and MS/MS methods

Determination of vortioxetine in human serum and saliva samples by HPLC–DAD and HPLC–MS

Contact Info

Product

Resources

About