Determination of midazolam (versed®) and its metabolites in plasma by high-performance liquid chromatography

Puglisi, Carl V.; Pao, J.; Ferrara, Frank J.; Silva, J.Arthur F. de

doi:10.1016/s0378-4347(00)82020-4

Cited by 55 publications

(9 citation statements)

References 12 publications

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“…Plasma samples from eight patients were also assayed for 1-hydroxymidazolam by high pressure liquid chromatography (HPLC). 18 The within-day cv was 11% at 4 g litre 91 and 3.1% at 10 g litre 91 , and the limit of detection was approximately 2 g litre 91 .…”

Section: Methodsmentioning

confidence: 92%

Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients

Björkman

Rigemar

Idvall

1997

British Journal of Anaesthesia

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The aim of this study was to determine the bioavailability and absorption kinetics of midazolam given as an intranasal (i.n.) spray. In addition, plasma concentrations of the active metabolite, 1-hydroxymidazolam, were measured to give an indication of enteral absorption. An i.v. and i.n. midazolam dose were given in a crossover study to 14 adult surgical patients. Individual uptake profiles of i.n. midazolam were estimated by numerical deconvolution. After an i.n. dose of 0.15 mg kg-1, maximum arterial plasma concentrations were 192 (SD 48) micrograms litre-1 at 14 (2) min. Uptake of midazolam was rapid and bioavailability was 83 (15)%. Formation of the 1-hydroxy metabolite after i.n. administration did not exceed that after the i.v. dose. This demonstrates that under optimal conditions absorption of midazolam via the nasal mucosa was virtually complete. In this case little midazolam was swallowed and subjected to first-pass metabolism in the liver and therefore pharmacologically important amounts of active metabolite were not produced. Routinely administering i.n. midazolam under the assumption that the bioavailability is approximately 50% (as reported previously in the literature) may lead to overdosing in some patients.

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Section: Methodsmentioning

confidence: 92%

Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients

Björkman

Rigemar

Idvall

1997

British Journal of Anaesthesia

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“…The concentrations of midazolam and 1′ -hydroxymidazolam in plasma were measured by HPLC as previously described with minor modification. 24 Briefly, 1 mL of 1 M sodium phosphate buffer (pH 9) and 3 mL of diethyl ether:methylene chloride (7:3, v/v) were added to the plasma sample (1 mL) containing nitrazepam (1 µg) as internal standard. After being shaken, the mixture was centrifuged at 3000g for 5 minutes.…”

Section: Methodsmentioning

confidence: 99%

Effects of Ginkgo Biloba Extract on Pharmacokinetics and Pharmacodynamics of Tolbutamide and Midazolam in Healthy Volunteers

Uchida¹,

Yamada

et al. 2006

The Journal of Clinical Pharma

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This study was undertaken to clarify the influence of repeated oral administration of Ginkgo biloba extract (GBE) on CYP2C9 and CYP3A4. CYP2C9 probe (tolbutamide, 125 mg) and CYP3A4 probe (midazolam, 8 mg) were orally administered to 10 male healthy volunteers before and after GBE intake (360 mg/d) for 28 days, and they received 75 g glucose after the dosing of tolbutamide. Plasma drug concentrations and blood glucose levels were measured. The area under concentration versus time curve (AUC0-infinity) for tolbutamide after GBE intake was slightly but significantly (16%) lower than that before GBE intake. Concomitantly, GBE tended to attenuate AUC0-2 of blood glucose-lowering effect of tolbutamide. AUC0-infinity for midazolam was significantly (25%) increased by GBE intake and oral clearance was significantly (26%) decreased. Thus, it is suggested that the combination of GBE and drugs should be cautious in terms of the potential interactions, especially in elderly patients or patients treated with drugs exerting relatively narrow therapeutic windows.

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“…Although LC-UV has been used for decades for the above purpose, these methodologies typically represent relatively poor sensitivity and low throughput, with a reported sensitivity of 1.0-100 ng/mL, sample size of up to 2.0 mL, and analysis cycle time of up to 18 min (Blackett et al, 1988;Carrillo et al, 1998;El Mahjoub and Staub, 2000;Ha et al, 1993;Johnson et al, 2002;Lee and Charles, 1996;Odou et al, 1997;Mastey et al, 1994;Portier et al, 1999;Puglisi et al, 1985;Sautou et al, 1991;ter Horst et al, 2003;van Brandt et al, 1997;Vletter et al, 1990;Yasui-Furukori et al, 2004). GC-MS methods appear to be more sensitive than HPLC-UV with a reported LLOQ of 20 pg/ mL for both midazolam and 1′-hydroxymidazolam when 1 mL of human plasma was used.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of midazolam and 1′‐hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

Li¹,

Luo²,

Smith³

et al. 2007

Biomedical Chromatography

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A sensitive and simple liquid chromatography-tandem mass spectrometry method for the determination of midazolam and 1'-hydroxymidazolam in human plasma has been developed and validated with a dynamic range of 0.1-250 ng/mL. The analysis was based on semi-automated liquid-liquid extraction followed by evaporation of the extraction solvent, reconstitution and chromatography on a reversed-phase C(18) column. The mobile phase consists of 5 mm ammonium acetate and methanol and runs in gradient at a flow rate of 0.25 mL/min with column temperature of approximately 20 degrees C. The entire column effluent was transferred into the LC-MS/MS interface operated in positive electrospray ionization mode. The chromatographic run time was 4.3 min per injection, with retention times for midazolam, 1'-hydroxymidazolaml and the internal standard, triazolam, of 2.5, 2.3 and 2.1 min, respectively. The intra-day and inter-day precision (RSD %) and accuracy (bias %) of the quality control samples were <15.0% and within +/-13%, respectively. The current method has been applied to a clinical drug-drug interaction study in human.

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Determination of midazolam (versed®) and its metabolites in plasma by high-performance liquid chromatography

Cited by 55 publications

References 12 publications

Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients

Pharmacokinetics of midazolam given as an intranasal spray to adult surgical patients

Effects of Ginkgo Biloba Extract on Pharmacokinetics and Pharmacodynamics of Tolbutamide and Midazolam in Healthy Volunteers

Simultaneous determination of midazolam and 1′‐hydroxymidazolam in human plasma by liquid chromatography with tandem mass spectrometry

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