Simultaneous determination of blood concentrations of methohexital and its hydroxy metabolite by gas chromatography and identification of 4′-hydroxymethohexital by combined gas—liquid chromatography—mass spectrometry

Heusler, H.; Epping, J.; Heusler, S; Richter, E.; Vermeulen, Nico; Breimer, D. D.

doi:10.1016/s0378-4347(00)86074-0

Cited by 15 publications

(6 citation statements)

References 8 publications

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“…This was a modification of the procedure described by Le Normand and colleagues [9]. The extraction was performed according to the method of Heusler and colleagues [10]. Plasma 1 ml was mixed with internal standard (propoxate) and solvent 10 ml (ether: n-hexan: isoamylalcohol 50: 50:2).…”

Section: Plasma Analytical Proceduresmentioning

confidence: 99%

Hepatic Disposition of Methohexitone in Patients Undergoing Coronary Bypass Surgery

Lange

Stephan

Brand

et al. 1992

British Journal of Anaesthesia

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In order to clarify the relative contribution of hepatic metabolism to the short term disposition of methohexitone, we have measured hepatic blood flow during induction of anaesthesia with a 1.5-mg kg-1 i.v. bolus dose of methohexitone. Median hepatic clearance was 1.01 litre min-1 and hepatic extraction 87%. As a consequence of the high hepatic extraction, the hepatic clearance of methohexitone was closely dependent on hepatic plasma flow.

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Section: Plasma Analytical Proceduresmentioning

confidence: 99%

Hepatic Disposition of Methohexitone in Patients Undergoing Coronary Bypass Surgery

Lange

Stephan

Brand

et al. 1992

British Journal of Anaesthesia

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“…The blood samples were centrifuged and plasma stored at -20 °C until assay. Methohexitone and its 4'-hydroxy metabolite concentrations were measured by gas-liquid chromatography with nitrogen-selective detection, after slight modifications to the original procedure [9]. Briefly, 0.2-1.0 ml samples of plasma were adjusted to pH 6.5 with Na 2 HPO 4 solution and extracted with cyclohexane: dichloromethane (1:1) 4 ml after addition of hexobarbitone 2 jig as internal standard.…”

Section: Assay Of Methohexitonementioning

confidence: 99%

“…Briefly, 0.2-1.0 ml samples of plasma were adjusted to pH 6.5 with Na 2 HPO 4 solution and extracted with cyclohexane: dichloromethane (1:1) 4 ml after addition of hexobarbitone 2 jig as internal standard. After evaporation of the solvents, the extracts were injected onto a gas chromatograph with an OV-17 packed column as described [9]. The coefficient of variation of the assay was around 4% over the range 0.13-2 ug per sample.…”

Section: Assay Of Methohexitonementioning

confidence: 99%

“…The coefficient of variation of the assay was around 4% over the range 0.13-2 ug per sample. The metabolite was identified by its chromatographic retention time relative to those of methohexitone and hexobarbitone [9], and by its presence only in plasma and urine samples from patients treated with methohexitone. As we did not have access to pure metabolite, it could not be assayed in absolute concentrations; however, its terminal half-life could be calculated from concentrations expressed in arbitrary units (peak height of metabolite vs that of the internal standard).…”

Section: Assay Of Methohexitonementioning

confidence: 99%

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Pharmacokinetics and Clinical Experience of 20-H Infusions of Methohexitone in Intensive Care Patients With Postoperative Pyrexia

Redke

Björkman

Rosberg

1991

British Journal of Anaesthesia

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We have studied the pharmacokinetics of 20-h infusions of methohexitone in young patients with postoperative fever undergoing artificial ventilation of the lungs. The infusion rate was adjusted so that patients were unresponsive to vocal stimulation but reacted to tracheal suction. The mean steady state concentration of methohexitone required was 2.6 mg litre-1 (unbound 0.53 mg litre-1). The mean (SD) total clearance of methohexitone was 16.3 (4.2) ml min-1 kg-1, which is greater than that for volunteers or normal surgical patients. The unbound clearance correlated positively with body temperature during the infusion (r = 0.796, P = 0.017). The terminal half-life of methohexitone was 6.3 (3.8) h and that of the 4'-hydroxy metabolite 5.8 (2.1) h. There were no marked haemodynamic effects of the infusion, and no excessive sedation after the infusion. However, the clearance of methohexitone was high and variable, possibly as a direct effect of postoperative fever. Consequently, the need for individual titration of the rate of infusion is emphasized.

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“…Several methods for the determination of methohexital and its metabolites in biological fluids have been reported using HPLC (Bjorkman and Idvall, 1984), GLC with (Breimer and Van Rossum, 1974;Bjorkman et al, 1983) or without selective detection (Sunshine et al, 1966), or mass spectrometry (Heusler et al, 1981). We developed an assay in which the use of a WCOT fused-silica capillary column and nitrogen-specific detection offered good sensitivity for precisely measuring both low and toxic plasma concentrations.…”

Section: Introductionmentioning

confidence: 99%

Quantitative Analysis of Serum Methohexital by GLC Using Capillary Column and Nitrogen‐selective Detection

Normand

Villepoix

Athouel

et al. 1988

Fundamemntal Clinical Pharma

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A gas chromatographic method for routine quantitation of methohexital in plasma samples is reported. One-step extraction in organic phase, the use of a fused silica capillary column, and nitrogen-selective detection permit simple, precise, and sensitive determination of methohexital in plasma. A linear relationship is described between peak height ratio and methohexital concentrations ranging from 0.125 to 50.0 micrograms/ml (r = 0.998). The sensitivity limit of the assay was 6 ng/ml in plasma. No interfering peak was observed with numerous other drugs. The procedure was successfully applied to the determination of pharmacokinetic parameters of methohexital after IV administration or continuous infusion in a child and an adult.

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Simultaneous determination of blood concentrations of methohexital and its hydroxy metabolite by gas chromatography and identification of 4′-hydroxymethohexital by combined gas—liquid chromatography—mass spectrometry

Cited by 15 publications

References 8 publications

Hepatic Disposition of Methohexitone in Patients Undergoing Coronary Bypass Surgery

Hepatic Disposition of Methohexitone in Patients Undergoing Coronary Bypass Surgery

Pharmacokinetics and Clinical Experience of 20-H Infusions of Methohexitone in Intensive Care Patients With Postoperative Pyrexia

Quantitative Analysis of Serum Methohexital by GLC Using Capillary Column and Nitrogen‐selective Detection

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