Sensitive, specific quantitative analysis of tacrolimus (FK506) in blood by liquid chromatography-electrospray tandem mass spectrometry

1996 ◽  
Vol 42 (2) ◽  
pp. 279-285 ◽  
Author(s):  
P J Taylor ◽  
A Jones ◽  
G A Balderson ◽  
S V Lynch ◽  
R L Norris ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Complex Mixture ◽  
Turnaround Time ◽  
Pharmacokinetic Studies ◽  
Tandem Mass ◽  
Blood Concentrations ◽  
Liquid Chromatography Tandem Mass ◽  
The Difference

Abstract The capacity of liquid chromatography-tandem mass spectrometry (LC-MS2) to detect and define individual components in a complex mixture has been utilized to develop a quantitative assay of the potent immunosuppressant drug, tacrolimus. Trough blood concentrations were measured in 175 samples obtained over several weeks after liver transplantation from seven patients. The assay was linear over the range of 0.2 to 100 micrograms/L. Imprecision was <8%, and accuracy was 99-101%. The turnaround time for a batch of 20 samples was 2.5 h. No interference from any of the other drugs being administered to the patients was evident. An ELISA also performed on the same samples overestimated the concentrations substantially, as indicated by a plot of the difference between the results for the two methods vs their mean. The favorable characteristics of the LC-MS2 assay, especially its sensitivity and specificity, will facilitate detailed pharmacokinetic studies of tacrolimus, particularly under circumstances in which metabolism is perturbed by either hepatic dysfunction or drug interactions.

scholarly journals Determination of Tissue Distribution of Alisol G, a CB1R Antagonist, in Rats by Ultra-High-Performance Liquid Chromatography-Tandem Mass Spectrometry

2021 ◽  
Author(s):  
Chen-Yu Gao ◽  
Jian-Qiang Xi ◽  
Ding-Zhong Song ◽  
Jie Yuan ◽  
Wu-Si Hao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
High Performance ◽  
Tandem Mass ◽  
Blood Concentrations ◽  
Therapeutic Benefits ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

AbstractPeripheral CB1R blockers without crossing the blood–brain barrier (BBB) have demonstrated therapeutic benefits in metabolic syndromes, including obesity. Among them is Alisol G, a tetracyclic triterpene from Alismatis rhizoma (zexie), which can effectively reduce the weight of obese mice. Results from CP55940-induced [35S] GTPγS cannabinoid-type 1 receptor (CB1R) binding assay show an IC50 of 34.8 μmol/L for Alisol G, implicating its role as a CB1R antagonist. The purpose of our study is to assess whether Alisol G could serve as a peripheral CB1R antagonist for obesity treatment. In this study, we build a simple, reliable, and sensitive method to detect the concentration of Alisol G in rat tissue by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). The results showed that Alisol G was mainly distributed in intestinal midgut, mucosa and small intestine, with little brain exposure. We suggested that intestine may be the main acting sites of Alisol G. Through comparison of brain and blood concentrations of Alisol G, our data showed that Alisol G cannot penetrate the BBB easily. In conclusion, Alisol G may represent a peripheral CB1R antagonist for the further treatment of obesity.

scholarly journals A Hydrophilic Interaction Liquid Chromatography–Tandem Mass Spectrometry Quantitative Method for Determination of Baricitinib in Plasma, and Its Application in a Pharmacokinetic Study in Rats

Molecules ◽  
2020 ◽  
Vol 25 (7) ◽  
pp. 1600 ◽  
Author(s):  
Essam Ezzeldin ◽  
Muzaffar Iqbal ◽  
Yousif A. Asiri ◽  
Azza A Ali ◽  
Prawez Alam ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Janus Kinase ◽  
Pharmacokinetic Studies ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Baricitinib, is a selective and reversible Janus kinase inhibitor, is commonly used to treat adult patients with moderately to severely active rheumatoid arthritis (RA). A fast, reproducible and sensitive method of liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the quantification of baricitinib in rat plasma has been developed. Irbersartan was used as the internal standard (IS). Baracitinib and IS were extracted from plasma by liquid–liquid extraction using a mixture of n-hexane and dichloromethane (1:1) as extracting agent. Chromatographic separation was performed using Acquity UPLC HILIC BEH 1.7 µm 2.1 × 50 mm column with the mobile phase consisting of 0.1% formic acid in acetonitrile and 20 mM ammonium acetate (pH 3) (97:3). The electrospray ionization in the positive-mode was used for sample ionization in the multiple reaction monitoring mode. Baricitinib and the IS were quantified using precursor-to-production transitions of m/z 372.15 > 251.24 and 429.69 > 207.35 for baricitinib and IS, respectively. The method was validated according to the recent FDA and EMA guidelines for bioanalytical method validation. The lower limit of quantification was 0.2 ng/mL, whereas the intra-day and inter-day accuracies of quality control (QCs) samples were ranged between 85.31% to 89.97% and 87.50% to 88.33%, respectively. Linearity, recovery, precision, and stability parameters were found to be within the acceptable range. The method was applied successfully applied in pilot pharmacokinetic studies.

Enantioselective determination of lercanidipine in human plasma for pharmacokinetic studies by normal-phase liquid chromatography–tandem mass spectrometry

2003 ◽  
Vol 796 (2) ◽  
pp. 429-437 ◽  
Author(s):  
Valquiria Aparecida Polisel Jabor ◽  
Eduardo Barbosa Coelho ◽  
Demian Rocha Ifa ◽  
Pierina Sueli Bonato ◽  
Neife Aparecida Guinaim dos Santos ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Normal Phase ◽  
Pharmacokinetic Studies ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass ◽  
Phase Liquid

Method Validation of Seven Synthetic Cathinones by LC–MS-MS Analysis and the Prevalence of N-Ethylpentylone in Postmortem Casework

2020 ◽  
Author(s):  
Alexander D Giachetti ◽  
Joseph H Kahl ◽  
M Elizabeth Zaney ◽  
George W Hime ◽  
Diane M Boland
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Solid Phase ◽  
Synthetic Cathinones ◽  
Medical Examiner ◽  
Tandem Mass ◽  
Blood Concentrations ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Abstract N-ethylpentylone (NEP, ephylone, bk-EBDP) was the most prevalent synthetic cathinone detected by the Miami-Dade Medical Examiner Toxicology Laboratory from 2016 to 2018. There is limited information regarding the toxicity of NEP; however, the few published reports suggest that NEP can cause serious toxic effects and sudden death. The purpose of this publication is to describe a validated liquid chromatography-tandem mass spectrometry (LC–MS-MS) method for seven synthetic cathinones (methylone, ethylone, butylone, dibutylone, alpha-Pyrrolidinopentiophenone (α-PVP), pentylone and NEP) and to present a detailed summary regarding the presence of NEP in postmortem casework at the Miami-Dade Medical Examiner Department. Postmortem iliac blood, serum, liver and brain specimens were prepared by solid-phase extraction with analysis by ultra-high-performance liquid chromatography-tandem mass spectrometry. Analyte linearity was established from 0.01 to 0.5 mg/L on a six-point calibration curve. A total of 101 NEP quantitations were performed using this method. Concentrations in postmortem case samples ranged from 0.01 to 2.7 mg/L. Iliac blood concentrations averaged 0.312 mg/L with a median of 0.137 mg/L (n = 72) across all causes and manners of death. Approximately half of the cases were homicides in which the decedent was the victim of gunshot wounds or stabbing. Two of the three highest concentration cases of NEP (2.7 and 1.7 mg/L) involved 38-year-old white males who were tasered by police prior to death. The psychostimulant effect of NEP may result in an excited delirium and/or hallucinogenic state. The concentration of NEP detected in accidental intoxication and polydrug cases overlapped with those attributed to other causes, including homicides and police-involved deaths.

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