A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids

Hochhaus, Günther; Derendorf, Hartmut; Barth, Jürgen

doi:10.1016/0731-7085(91)80218-x

Cited by 11 publications

(2 citation statements)

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“…This approach was also necessary, as the selective extraction of D in the presence of DS failed, and a substantial amount of DS was extracted under these conditions. 7 Urine samples were assayed by RIA after extraction with ethyl acetate. Calibration curves were established for all assays under conditions identical to those of actual samples.…”

Section: Analytical Methods Employedmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Dexamethasone Sodium‐m‐Sulfobenzoate (DS) after Intravenous and Intramuscular Administration: A Comparison with Dexamethasone Phosphate (DP)

Hochhaus

Barth

Al-Fayoumi

et al. 2001

The Journal of Clinical Pharma

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The pharmacokinetics (PK) and pharmacodynamics (effects on blood lymphocytes) of dexamethasone (D) after intravenous (i.v.) administration of dexamethasone phosphate (DP, 10 mg, equivalent to 8.3 mg of dexamethasone) and after intravenous and intramuscular (i.m.) administration of dexamethasone sulfobenzoate sodium (DS, 9.15 mg, equivalent to 6 mg of dexamethasone) were assessed. Only 25% of DS was converted into dexamethasone with a half-life for DS of 5.4 hours and 7.4 hours after i.v. and i.m. administration, respectively. Consequently, the mean residence time of D after both i.m. and i.v. administration of DS (10.4-11.6 h) was longer than that after DP administration (6.1 h). The smaller lymphocyte suppression induced by DS (50% of that after DP administration) was shown to be related to differences in the pharmacokinetics. This study revealed significant differences in the pharmacokinetics of D after administration of DS and DP and stresses the importance of the prodrug for the pharmacological response. Because of the slow and incomplete conversion of DS into dexamethasone, its use in emergency medicine situations should be critically evaluated.

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Section: Analytical Methods Employedmentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Dexamethasone Sodium‐m‐Sulfobenzoate (DS) after Intravenous and Intramuscular Administration: A Comparison with Dexamethasone Phosphate (DP)

Hochhaus

Barth

Al-Fayoumi

et al. 2001

The Journal of Clinical Pharma

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“…However, they either lack the sensitivity needed for detecting levels that are seen with budesonide or the selectivity due to interfering endogenous steroids or budesonide metabolites. Alternative methods like HPLC/ RIA have been used but they are very time-consuming (Hochhaus et al, 1991(Hochhaus et al, , 1998. Recently, liquid chromatography-mass spectrometric assays (LC/MS) have been developed for the analysis of budesonide (Lindberg et al, 1992;Kronkvist et al, 1993Kronkvist et al, , 1998Li et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

SPE/RIA vs LC/MS for measurement of low levels of budesonide in plasma

Dimova

Wang

Pommery

et al. 2002

Biomedical Chromatography

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A radioimmunoassay is described that measures budesonide in plasma after solid-phase extraction (SPE/RIA) of the analyte. The performance of the assay was compared with that of a selective LC/MS method. The limit of quantitation of budesonide determined for the LC/MS and SPE/RIA assay was 50 pg/mL and 120 pg/mL, respectively. Based on quality control samples, a higher variability was observed for the SPE/RIA (CV between 4.5 and 23.0%) than for the LC/MS method (CV between 7.5 and 12.5%). Plasma samples obtained from healthy volunteers after administration of budesonide rectal foam were assayed by both methods. In a subset of samples, these results were compared with those measured by direct RIA to evaluate the selectivity of two assays. About two times higher budesonide levels were measured with the direct RIA (lacking the extraction step), presumably because of cross-reactivity with budesonide metabolites, indicating that the extraction step in SPE/RIA is necessary for selectivity. Both SPE/RIA and LC/MS methods were found to be selective, sensitive and suitable for pharmacokinetic studies. Results obtained from the two methods were compared with a number of statistical methods. Ratios of results obtained for the clinical samples were close to 1 (ratio LC-MS/ SPE/RIA = 0.98 +/- 0.27). Linear regression indicated a slope of 1.17 +/- 0.0378. The concordance correlation (r = 0.91) indicated that the agreement between both methods was fair while the Bland-Altman plot indicated that the agreement was less pronounced at higher concentrations (1-3 ng/mL). In summary, the results confirm that the SPE/RIA is an alternative to HPLC/MS and that among the statistical methods tested the concordance correlation analysis was judged to be the most informative test to assess the comparability of two methods.

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Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

et al. 2017

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The first example of a Cu-catalyzed and 4-OH-TEMPO mediated intermolecular [3 + 3] annulation of saturated ketones with b-enamino esters is reported herein, which was successfully used for the synthesis of versatile nicotinates through sequential b-C(sp 3 )-H bond alkenylation, enaminecarbonyl condensation and aromatization. This protocol tolerates a variety of functional groups, thereby providing a practical and efficient method for the fabrication of 5H-chromeno[4,3-b]pyridin-5one skeletons.

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A selective LC/RIA for dexamethasone and its prodrug dexamethasone-21-isonicotinate in biological fluids

Cited by 11 publications

References 10 publications

Pharmacokinetics and Pharmacodynamics of Dexamethasone Sodium‐m‐Sulfobenzoate (DS) after Intravenous and Intramuscular Administration: A Comparison with Dexamethasone Phosphate (DP)

Pharmacokinetics and Pharmacodynamics of Dexamethasone Sodium‐m‐Sulfobenzoate (DS) after Intravenous and Intramuscular Administration: A Comparison with Dexamethasone Phosphate (DP)

SPE/RIA vs LC/MS for measurement of low levels of budesonide in plasma

Copper Catalysis for Nicotinate Synthesis through β‐Alkenylation/Cyclization of Saturated Ketones with β‐Enamino Esters

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