Development and validation of an LC-MS-MS method for the determination of terfenadine in human plasma

Xu, Allan; Linderholm, K.; Peng, Li-Qing; Hulse, James D.

doi:10.1016/0731-7085(96)01804-3

Cited by 19 publications

(4 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The reported quantitation limits corresponded to a signal to noise ratio of approximately 10. The methodology described below was adapted from these publications [65, 66].…”

Section: Methodsmentioning

confidence: 99%

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system

et al. 2018

View full text Add to dashboard Cite

Regulation of cosmetic testing and poor predictivity of preclinical drug studies has spurred efforts to develop new methods for systemic toxicity. Current in vitro assays do not fully represent physiology, often lacking xenobiotic metabolism. Functional human multi-organ systems containing iPSC derived cardiomyocytes and primary hepatocytes were maintained under flow using a low-volume pumpless system in a serum-free medium. The functional readouts for contractile force and electrical conductivity enabled the non-invasive study of cardiac function. The presence of the hepatocytes in the system induced cardiotoxic effects from cyclophosphamide and reduced them for terfenadine due to drug metabolism, as expected from each compound's pharmacology. A computational fluid dynamics simulation enabled the prediction of terfenadine-fexofenadine pharmacokinetics, which was validated by HPLC-MS. This in vitro platform recapitulates primary aspects of the in vivo crosstalk between heart and liver and enables pharmacological studies, involving both organs in a single in vitro platform. The system enables non-invasive readouts of cardiotoxicity of drugs and their metabolites. Hepatotoxicity can also be evaluated by biomarker analysis and change in metabolic function. Integration of metabolic function in toxicology models can improve adverse effects prediction in preclinical studies and this system could also be used for chronic studies as well.

show abstract

“…The reported quantitation limits corresponded to a signal to noise ratio of approximately 10. The methodology described below was adapted from these publications [65, 66].…”

Section: Methodsmentioning

confidence: 99%

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The plasma concentrations of bepridil and terfenadine (10,11) were determined using LC / MS/ MS [HP1100 (Agilent Technologies, Aalo Alto, CA, USA), API 365 and API 3000 (Applied Biosystems / MDS SCIEX, Foster City, CA, USA), or 7000 Series (Hitachi, Ltd., Tokyo)].…”

Section: Determination Of the Plasma Concentrations Of The Test Compomentioning

confidence: 99%

QT PRODACT: In Vivo QT Assay With a Conscious Monkey for Assessment of the Potential for Drug-Induced QT Interval Prolongation

Ando

Hombo

Kanno³

et al. 2005

J Pharmacol Sci

View full text Add to dashboard Cite

Abstract. In safety pharmacology studies, the effects on the QT interval of electrocardiograms are routinely assessed using a telemetry system in cynomolgus monkeys. However, there is a lack of integrated databases concerning in vivo QT assays in conscious monkeys. As part of QT Interval Prolongation: Project for Database Construction (QT PRODACT), the present study examined 10 positive compounds with the potential to prolong the QT interval and 6 negative compounds considered to have no such effect on humans. The experiments were conducted at 7 facilities in accordance with a standard protocol established by QT PRODACT. The vehicle or 3 doses of each test compound were administered orally to male cynomolgus monkeys (n = 3 -4), and telemetry signals were recorded for 24 h. None of the negative compounds prolonged the corrected QT using Bazett's formula (QTcB) interval. On the other hand, almost all of the positive compounds prolonged the QTcB interval, but haloperidol, terfenadine, and thioridazine did not. The failure to detect the QTcB interval prolongation appeared to be attributable for the differences in metabolism between species and / or disagreement with Bazett's formula for tachycardia. In the cynomolgus monkeys, astemizole induced Torsade de Pointes and cisapride caused tachyarrhythmia at lower plasma concentrations than those observed in humans and dogs. These results suggest that in vivo QT assays in conscious monkeys represent a useful model for assessing the risks of drug-induced QT interval prolongation. Supplementary material (Appendix): available only at http://dx

show abstract

“…Electrospray LC/MS/MS methods have recently been widely used for drug analysis in biological media, especially in the pharmaceutical industry [9][10][11][12][13][14][15][16][17][18]. These methods are generally highly sensitive and specific, and they simplify the sample cleanup.…”

Section: Discussionmentioning

confidence: 99%

An API LC/MS/MS quantitation method for ansamitocin P-3 (AP3) and its preclinical pharmacokinetics

Liu¹,

Floss²,

Cassady³

et al. 2004

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

Development and validation of an LC-MS-MS method for the determination of terfenadine in human plasma

Cited by 19 publications

References 5 publications

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system

Investigation of the effect of hepatic metabolism on off-target cardiotoxicity in a multi-organ human-on-a-chip system

QT PRODACT: In Vivo QT Assay With a Conscious Monkey for Assessment of the Potential for Drug-Induced QT Interval Prolongation

An API LC/MS/MS quantitation method for ansamitocin P-3 (AP3) and its preclinical pharmacokinetics

Contact Info

Product

Resources

About