Analysis of betamethasone in rat plasma using automated solid-phase extraction coupled with liquid chromatography–tandem mass spectrometry. Determination of plasma concentrations in rat following oral and intravenous administration

Tamvakopoulos, Constantin; Neugebauer, J.; Donnelly, Marcie J.; Griffin, Patrick R.

doi:10.1016/s1570-0232(02)00271-4

Cited by 29 publications

(17 citation statements)

References 11 publications

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“…We therefore used the HLB Oasis cartridge format for extracting plasma samples, which involved a 10-fold larger sample volume (500 versus 50 l). By using a larger sample volume, we were able to reduce the assay lower limit of quantification of 2 ng/ml, reported by Tamvakopoulos et al (2002), to 0.1 ng/ml. During the preparation of this article, two other methods describing LC/ MS/MS analysis of betamethasone in plasma were published (Taylor et al, 2004;Luo et al, 2005).…”

Section: Samtani Et Almentioning

confidence: 89%

“…2). The assay was adapted from a method described for rat plasma samples (Tamvakopoulos et al, 2002). An important change was made wherein the assay was scaled up to make it suitable for plasma samples from sheep.…”

Section: Lc/ms/ms Analysis For Betamethasonementioning

confidence: 99%

“…An important change was made wherein the assay was scaled up to make it suitable for plasma samples from sheep. Tamvakopoulos et al (2002) Petersen et al (1983). c Ratio of the clinical dose (0.17 mg/kg) to the studied dose (0.25 mg/kg).…”

Section: Lc/ms/ms Analysis For Betamethasonementioning

confidence: 99%

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Betamethasone Pharmacokinetics After Two Prodrug Formulations in Sheep: Implications for Antenatal Corticosteroid Use

Samtani

Löhle²,

Grant³

et al. 2005

Drug Metab Dispos

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ABSTRACT:Maternal administration of betamethasone to enhance fetal lung maturation for women who threaten preterm labor is common clinical practice. However, recommendations regarding the choice of betamethasone formulations for perinatal use are vague. The disposition of betamethasone from two commonly used antenatal formulations is poorly understood. We therefore designed a study to capture the true pharmacokinetic profiles of betamethasone from these fast acting and dual-release formulations. Betamethasone in sheep plasma was measured by a newly designed, highly sensitive liquid chromatography/tandem mass spectrometry assay after intramuscular injection (n ‫؍‬ 4) of 0.25 mg/kg betamethasone phosphate and 0.5 mg/kg betamethasone phosphate/acetate formulations. Compartmental modeling was performed using the ADAPT II program. Betamethasone pharmacokinetics could be captured for 24 h for the phosphate and for 5 days for the phosphate/acetate formulations. The phosphate formulation profile had the appearance of a traditional Bateman function with a terminal half-life of 4 h, whereas the phosphate/acetate formulation produced a biexponential decline with a terminal half-life of 14 h. The latter is much longer than is commonly reported and has been missed in the literature due to assay limitations. Extrapolations to humans indicate that although both formulations might have similar therapeutic indices, the dual formulation might be associated with a lower safety profile. In light of this newly identified long terminal half-life for the betamethasone dual formulation, dosing practices for betamethasone in pregnancy need to be reassessed.Preterm birth occurs in about 10% of pregnancies, and complications associated with prematurity, especially respiratory distress syndrome, are the leading cause of mortality in prematurely born infants (NIH Consensus Panel, 1995). Betamethasone is administered maternally to enhance fetal lung maturation in women who threaten preterm labor during 24 to 34 weeks gestation. The National Institutes of Health recommends administration of two maternal intramuscular injections of 12-mg betamethasone 24 h apart for this condition. Although the doses of betamethasone are stated, the exact formulation recommendation is not clear. Betamethasone is available as a fast releasing phosphate ester prodrug formulation and as a dual acting suspension formulation containing phosphate and acetate ester prodrugs. Both formulations have been tested in clinical trials and have been shown to be efficacious in producing precocious fetal lung maturation (Liggins and Howie, 1972;Gamsu et al., 1989). However, there is controversy regarding the betamethasone-releasing properties of the acetate prodrug, and a recent meta-analysis suggests that this prodrug is probably of little therapeutic benefit for antenatal use (Jobe and Soll, 2004). Although the release properties of the acetate prodrug have been questioned, long-duration studies looking at the release pattern of betamethasone from this prodrug do not exist. ...

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Section: Samtani Et Almentioning

confidence: 89%

Section: Lc/ms/ms Analysis For Betamethasonementioning

confidence: 99%

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Betamethasone Pharmacokinetics After Two Prodrug Formulations in Sheep: Implications for Antenatal Corticosteroid Use

Samtani

Löhle²,

Grant³

et al. 2005

Drug Metab Dispos

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“…With an average body weight of 60 kg, this implies 2 Â 0.2 mg/kg of betamethasone within 24 h. In pregnant women, betamethasone half-life is approximately 4.5 h (Petersen et al, 1983), so the interval between the doses is about five half-lives. In rats, betamethasone half-life is approximately 2 h (Tamvakopoulos et al, 2002). Thus, in our treatment paradigm in rats, we delivered twice as much betamethasone as in the human treatment paradigm, separated by five half-lives.…”

Section: Animals and Prenatal Treatmentsmentioning

confidence: 99%

“…Although we did not measure plasma concentrations, available data after a single i.v. injection of 1 mg/kg of betamethasone in rats show that after 2 h its plasma concentration is around 1 mM and after 8 h it drops to 100 nM (Tamvakopoulos et al, 2002). However, in women, 24 h after the last injection of betamethasone, the plasma concentration is approximately 7 ng/ml (14 nM) (Anderson et al, 1977).…”

Section: Animals and Prenatal Treatmentsmentioning

confidence: 99%

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Velı́šek

2006

Neuropsychopharmacol

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Repeated antenatal administration of betamethasone is frequently used as a life-saving treatment in obstetrics. However, limited information is available about the outcome of this therapy in children. The initial prospective studies indicate that there are behavioral impairments in children exposed to repeated courses of prenatal betamethasone during the third trimester of pregnancy. In this study, pregnant rats received two betamethasone injections on day 15 of gestation. Using immunohistochemistry, the expression of a powerful anxiolytic molecule neuropeptide Y (NPY) was determined on postnatal day (PN) 20 in the hippocampus and basolateral amygdala (structures related to anxiety and fear) of the offspring. Prenatal betamethasone exposure induced significant increases in NPY expression in the hippocampus but not in the amygdala. Indeed, behavioral tests in the offspring, between PN20 and PN22 in the open field, on the horizontal bar, and in the elevated plus maze, indicated decreases in anxiety, without impairments in motor performance or total activity. Decreased body weight in betamethasone-exposed rats confirmed long-lasting effects of prenatal exposure. Thus, prenatal betamethasone treatment consistently increases hippocampal NPY, with decreases in anxiety-related behaviors and hippocampal role in anxiety in rats. Animal models may assist in differentiation between pathways of the desired main effect of the antenatal corticosteroid treatment and pathways of unwanted side effects. This differentiation can lead to specific therapeutic interventions directed against the side effects without eliminating the beneficial main effect of the corticosteroid treatment.

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Current Literature in Journal of Mass Spectrometry

2003

J. Mass Spectrom.

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In order to keep subscribers up‐to‐date with the latest developments in their field, John Wiley & Sons are providing a current awareness service in each issue of the journal. The bibliography contains newly published material in the field of mass spectrometry. Each bibliography is divided into 11 sections: 1 Books, Reviews & Symposia; 2 Instrumental Techniques & Methods; 3 Gas Phase Ion Chemistry; 4 Biology/Biochemistry: Amino Acids, Peptides & Proteins; Carbohydrates; Lipids; Nucleic Acids; 5 Pharmacology/Toxicology; 6 Natural Products; 7 Analysis of Organic Compounds; 8 Analysis of Inorganics/Organometallics; 9 Surface Analysis; 10 Environmental Analysis; 11 Elemental Analysis. Within each section, articles are listed in alphabetical order with respect to author (5 Weeks journals ‐ Search completed at 23rd. Oct. 2002)

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Analysis of betamethasone in rat plasma using automated solid-phase extraction coupled with liquid chromatography–tandem mass spectrometry. Determination of plasma concentrations in rat following oral and intravenous administration

Cited by 29 publications

References 11 publications

Betamethasone Pharmacokinetics After Two Prodrug Formulations in Sheep: Implications for Antenatal Corticosteroid Use

Betamethasone Pharmacokinetics After Two Prodrug Formulations in Sheep: Implications for Antenatal Corticosteroid Use

Prenatal Exposure to Betamethasone Decreases Anxiety in Developing Rats: Hippocampal Neuropeptide Y as a Target Molecule

Current Literature in Journal of Mass Spectrometry

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