scholarly journals A Sensitive Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study

Pharmaceutics ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 123 ◽  
Author(s):  
Lingzhi Wang ◽  
Do-Dang Phan ◽  
Nicholas Syn ◽  
Xiaoqiang Xiang ◽  
Hongyan Song ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Mouse Serum ◽  
Tandem Mass ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric

A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100 mm × 2.1 mm, 5 µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5–1000 ng/mL range. The intra- and inter-day precisions for nimbolide were ≤12.6% and ≤13.9% respectively. Intra-day accuracy ranged from 96.9–109.3%, while inter-day accuracy ranged from 94.3–110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum, and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy.

scholarly journals A Sensitive Liquid Chromatography-tandem Mass Spectrometry Method for the Determination of Nimbolide in Mouse Serum: Application to a Preclinical Pharmacokinetics Study

2018 ◽  
Author(s):  
Lingzhi Wang ◽  
Do-Dang Khoa Phan ◽  
Nicholas Syn ◽  
Xiaoqiang Xiang ◽  
Hongyan Song ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Mouse Serum ◽  
Tandem Mass ◽  
Liquid Chromatography Tandem Mass ◽  
Tandem Mass Spectrometric

A sensitive and robust liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated for the determination of nimbolide in mouse serum. Exemestane was used as the internal standard (IS). Here, we employed acetonitrile-based protein precipitation (PPT) for serum sample preparation, and performed chromatographic separation using an ODS Hypersil C18 column (100×2.1 mm, 5µm) with gradient elution (0.1% formic acid in water vs 100% acetonitrile). The run time was 6 min. Instrumental analysis was performed by electrospray ionization tandem mass spectrometry (ESI-MS/MS) in the multiple-reaction monitoring (MRM) under positive mode. A good linear calibration was achieved in the 5–1000 ng/ml range. The intra- and inter-day precisions for nimbolide were ≤ 12.6% and ≤ 13.9 % respectively. Intra-day accuracy ranged from 96.9% – 109.3% while inter-day accuracy ranged from 94.3% – 110.2%. The matrix effect of nimbolide, detected but consistent at low and high concentrations, do not affect linearity of standard curve. In conclusion, we have developed and validated a sensitive analytical method for determination of a novel natural compound nimbolide in mouse serum and it has been successfully applied to our preclinical study in investigating the pharmacokinetic properties of nimbolide, which could greatly facilitate the preclinical development of the promising lead compound for anticancer therapy.

scholarly journals Determination of Benzodiazepines in Urine Via Benzophenone Derivatives Using Liquid Chromatography-Tandem Mass Spectrometry

2010 ◽  
Vol 61 (4) ◽  
pp. 381-388 ◽  
Author(s):  
Robert Roškar ◽  
Marija Dolenc
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Tandem Mass ◽  
Standard Samples ◽  
Chromatography Tandem Mass Spectrometry ◽  
Liquid Chromatography Tandem Mass

Determination of Benzodiazepines in Urine Via Benzophenone Derivatives Using Liquid Chromatography-Tandem Mass SpectrometryThe aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confirmatory method.

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.

A fast, sensitive, and high throughput method for the determination of nintedanib in mouse plasma by UPLC-MS/MS

2015 ◽  
Vol 7 (16) ◽  
pp. 6561-6565 ◽  
Author(s):  
Dan Xu ◽  
Yang Zhang ◽  
Juji Dai ◽  
Yongyu Bai ◽  
Yuwu Xiao ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Internal Standard ◽  
Ultra Performance Liquid Chromatography ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
High Throughput Method ◽  
Liquid Chromatography Tandem Mass

A sensitive and rapid ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was developed to determine nintedanib in mice plasma using diazepam as the internal standard (IS).

scholarly journals Evaluation of a rapid micro-scale assay for tacrolimus by liquid chromatography-tandem mass spectrometry

2002 ◽  
Vol 39 (5) ◽  
pp. 487-492 ◽  
Author(s):  
BG Keevil ◽  
SJ McCann ◽  
DP Cooper ◽  
MR Morris
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Tandem Mass Spectrometry ◽  
Multiple Reaction Monitoring ◽  
Internal Standard ◽  
Immunosuppressive Drug ◽  
Tandem Mass ◽  
Chromatography Tandem Mass Spectrometry ◽  
Limit Of Quantitation ◽  
Liquid Chromatography Tandem Mass

Background: The immunosuppressive drug tacrolimus has complex and unpredictable pharmacokinetics, therefore regular monitoring is required in patients receiving tacrolimus therapy. We have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for measuring tacrolimus concentrations in whole blood and have compared it with a microparticle enzyme immunoassay. Methods: For the LC-MS/MS assay, samples were prepared in a 96-deep well microtitre plate by adding 10 µL of blood to 40 µL of 0·1 mol/L zinc sulphate solution. Proteins were precipitated by adding 100 µL acetonitrile containing ascomycin internal standard. After vigorous mixing and centrifugation, 20 µL of the supernatant was injected into the LC-MS/MS system. A C18 cartridge (3 mm × 4 mm) was eluted with a step gradient of 50% to 100% methanol containing 2 mmol/L ammonium acetate and 0·1% (v/v) formic acid, at 0·6 mL/min. The column was maintained at 55°C. Results: The retention times were 0·98 min for ascomycin and 0·98 min for tacrolimus. Cycle time was 2·5 min, injection to injection. The analytes were monitored using a Quattro micro tandem mass spectrometer operated in multiple reaction monitoring mode using the following transitions: m/z821 > 768 (tacrolimus) and m/z809 > 756 (ascomycin). The limit of quantitation was 0·5 µg/L and the assay was linear up to 30 µg/L. Precision of the method, over the concentration range 2·5-15·0 µg/L, was < 7% within-batch and < 6% between-batch. Total time to analyse 24 samples including result generation was 90 min. Conclusion: We conclude that the LC-MS/MS method is quick, precise and robust and will provide a fast turn around of results for the transplant physician.

Sign in / Sign up

Export Citation Format

Share Document