Rapid and simple gas—liquid chromatographic method for the determination of 5,5-dimethyl-2,4-oxazolidynedione

Gaździk, Wiesław R.; Kmiotek, Witold

doi:10.1016/s0378-4347(00)80747-1

Cited by 2 publications

(1 citation statement)

References 4 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Plasma was immediately separated by centrifugation. The samples were analyzed for DMO concentrations at the Department of Chemistry, The National Veterinary Institute, Uppsala, Sweden, according to the method of Gazdzik et al (30).…”

Section: Dose-and Concentration-dependent Effects On Embryonic Heart mentioning

confidence: 99%

Embryonic Arrhythmia by Inhibition of HERG Channels: A Common Hypoxia‐related Teratogenic Mechanism for Antiepileptic Drugs?

Azarbayjani

Danielsson

2002

Epilepsia

View full text Add to dashboard Cite

Summary:Purpose: There is evidence that drug-induced embryonic arrhythmia initiates phenytoin (PHT) teratogenicity. The arrhythmia, which links to the potential of PHT to inhibit a specific potassium channel (I kr ), may result in episodes of embryonic ischemia and generation of reactive oxygen species (ROS) at reperfusion. This study sought to determine whether the proposed mechanism might be relevant for the teratogenic antiepileptic drug trimethadione (TMO).Methods: Effects on embryonic heart rhythm during various stages of organogenesis were examined in CD-1 mice after maternal administration (125-1,000 mg/kg) of dimethadione (DMO), the pharmacologically active metabolite of TMO. Palatal development was examined after administration of a teratogenic dose of DMO and after simultaneous treatment with DMO and a ROS-capturing agent (␣-phenyl-N-tert-butylnitrone; PBN). The I kr blocking potentials of TMO and DMO were investigated in HERG-transfected cells by using voltage patch-clamping tests.Results: DMO caused stage-specific (gestation days 9-13 only) and dose-dependent embryonic bradycardia and arrhythmia at clinically relevant maternal plasma concentrations (3-11 mM). Hemorrhage in the nasopharyngeal part of the embryonic palate (within 24 h) preceded cleft palate in fetuses at term. Simultaneous treatment with PBN significantly reduced the incidence of DMO-induced cleft palate, from 40 to 13%. Voltage patch-clamping studies showed that particularly DMO (70% inhibition), but also TMO, had I kr blocking potential at clinically relevant concentrations.Conclusions: TMO teratogenicity, in the same way as previously shown for PHT, was associated with I kr -mediated episodes of embryonic cardiac arrhythmia and hypoxia/ reoxygenation damage.

show abstract

Section: Dose-and Concentration-dependent Effects On Embryonic Heart mentioning

confidence: 99%

Embryonic Arrhythmia by Inhibition of HERG Channels: A Common Hypoxia‐related Teratogenic Mechanism for Antiepileptic Drugs?

Azarbayjani

Danielsson

2002

Epilepsia

View full text Add to dashboard Cite

show abstract

Rapid and simple HPLC determination of 5,5‐dimethyl‐2,4‐oxazolidynedione in rabbit serum

Gaździk

Filipek

Kmiotek

1987

Biomedical Chromatography

Self Cite

View full text Add to dashboard Cite

A new method for the determination of 5,5-dimethyl-2,4-oxazolidynedione (DMO) in rabbit serum by reversed phase-HPLC with UV detection is described. The determination of DMO is performed without derivatisation. The internal standard is 5,5-diethylbarbituric acid (barbital). The method is rapid and simple with sensitivity limit of 20 ng/mL, high recovery (above 92%) and is suitable for pharmacokinetic studies.

show abstract

Rapid and simple gas—liquid chromatographic method for the determination of 5,5-dimethyl-2,4-oxazolidynedione

Cited by 2 publications

References 4 publications

Embryonic Arrhythmia by Inhibition of HERG Channels: A Common Hypoxia‐related Teratogenic Mechanism for Antiepileptic Drugs?

Embryonic Arrhythmia by Inhibition of HERG Channels: A Common Hypoxia‐related Teratogenic Mechanism for Antiepileptic Drugs?

Rapid and simple HPLC determination of 5,5‐dimethyl‐2,4‐oxazolidynedione in rabbit serum

Contact Info

Product

Resources

About