High performance liquid chromatographic assay for the simultaneous determination of midazolam and ketoconazole in plasma

Hamdy, Dalia A.; Brocks, Dion R.

doi:10.1016/j.jpba.2010.04.018

Cited by 20 publications

(19 citation statements)

References 26 publications

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“…Thus far the only stereoselective kinetic data that we know of in the literature is based on two rats which were used to illustrate applicability of the assay method. Similar to those rats, 24 all rats examined here, regardless of route of administration and dose, showed a high level of stereoselectivity in the plasma concentrations ( Table 1, Figs. 2 and 3).…”

Section: Discussionsupporting

confidence: 80%

“…A validated stereospecific HPLC method was used for measurements of KTZ enantiomers concentrations in each blood or plasma sample. 24 The validated lower limit of quantitation was 62.5 ng/mL for both enantiomers based on 0.1 mL of blood or plasma. Volumes of plasma assayed in samples from the pharmacokinetics study ranged between 75 and 150 lL.…”

Section: Assaymentioning

confidence: 98%

“…22,23 Recently, the first HPLC method for the determination of KTZ enantiomers in biological specimens was published. 24 The assay has now been applied to a pharmacokinetic study of (6)-KTZ in the rat and pharmacokinetic data of KTZ enantiomers after oral and iv administration of the drug are reported here.…”

mentioning

confidence: 99%

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Nonlinear stereoselective pharmacokinetics of ketoconazole in rat after administration of racemate

Hamdy

Brocks

2008

Chirality

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The stereoselective pharmacokinetics of ketoconazole (KTZ) enantiomers were studied in rat after i.v. and oral administration of (+/-)-KTZ. Sprague-Dawley rats were administered racemic KTZ as 10 mg/kg i.v. or orally over the range 10-80 mg/kg as single doses. Serial blood samples were collected over a 24-h period via surgically placed jugular vein cannulae. Plasma was assayed for KTZ enantiomer concentrations using stereospecific HPLC. Enantiomeric plasma protein binding was determined using an erythrocyte partitioning method at racemic concentrations of 10 and 40 mg/L. Stereoselective metabolism was tested by incubating the racemate (0.5-250 microM) with rat liver microsomes. In all rats, (+)-KTZ plasma concentrations were higher (up to 2.5-fold) than (-)-KTZ. The clearance and volume of distribution of the (-) enantiomer were approximately twofold higher than antipode. Half-life did not differ between the enantiomers. After oral doses the t(max) was not stereoselective. For both enantiomers with higher doses the respective half-life were found to increase. The mean unbound fraction of the (-) enantiomer was found to be up to threefold higher than that of the (+) enantiomer. At higher concentrations nonlinearity in plasma protein binding was observed for both enantiomers. There was no evidence of stereoselective metabolism by liver microsomes. Stereoselectivity in KTZ pharmacokinetics is attributable to plasma protein binding, although other processes such as transport or intestinal metabolism may also contribute.

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Section: Discussionsupporting

confidence: 80%

Section: Assaymentioning

confidence: 98%

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Nonlinear stereoselective pharmacokinetics of ketoconazole in rat after administration of racemate

Hamdy

Brocks

2008

Chirality

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“…18,36 Here, the method was reapplied and fortunately this did not interfere with the nonstereospecific assay of MDZ and KTZ. 24 The sum of the unbound fraction of the two enantiomers in NL rats using the erythrocyte-binding technique closely matched the current values for the racemate using the ultrafiltration method. 13 The results of this study cannot be directly extrapolated to the clinical population because it employed an animal model of HL known to cause marked increases in lipoproteins beyond which would be seen in humans.…”

Section: Discussionsupporting

confidence: 70%

“…24 The validated lower limit of quantitation was 25 ng/mL for both drugs based on 0.1 mL plasma or buffer. Volumes of plasma assayed in samples from the pharmacokinetic studies ranged between 75 and 150 :L. Standard curves were prepared from similar drug-spiked matrices.…”

Section: Assaymentioning

confidence: 99%

Effect of hyperlipidemia on ketoconazole–midazolam drug–drug interaction in rat

Hamdy

Brocks

2011

Journal of Pharmaceutical Sciences

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Pharmacokinetics of dronedarone in rat using a newly developed high‐performance liquid chromatographic assay method

Jardan

Gabr

Brocks

2014

Biomedical Chromatography

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A sensitive and selective high-performance liquid chromatographic method for the determination of dronedarone in rat plasma was developed. Dronedarone was extracted using one-step liquid-liquid extraction. The separation of dronedarone was accomplished using a C18 analytical column. The mobile phase was composed of a combination of monobasic potassium phosphate and acetonitrile. The UV detection was at 254 nm for ethopropazine, the internal standard, and after its elution, changed to 290 nm for dronedarone detection. The total analytical run time was 20 min. Mean recovery was >80%; the assay had excellent linear relationships (>0.999) between peak height ratios and plasma concentrations; the lower limit of quantification 25 was ng/mL, based on 100 μL of rat plasma. Accuracy and precision were <18% over the concentration range of 25-500 ng/mL. The assay was applied successfully to the measurement of dronedarone plasma concentrations in rats given the drug orally.

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High performance liquid chromatographic assay for the simultaneous determination of midazolam and ketoconazole in plasma

Cited by 20 publications

References 26 publications

Nonlinear stereoselective pharmacokinetics of ketoconazole in rat after administration of racemate

Nonlinear stereoselective pharmacokinetics of ketoconazole in rat after administration of racemate

Effect of hyperlipidemia on ketoconazole–midazolam drug–drug interaction in rat

Pharmacokinetics of dronedarone in rat using a newly developed high‐performance liquid chromatographic assay method

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