Rapid determination of diazepam and nordiazepam in plasma by electron capture gas—liquid chromatography

Weinfeld, Robert E.; Posmanter, Howard N.; Khoo, Ko‐Chin; Puglisi, Carl V.

doi:10.1016/s0378-4347(00)81313-4

Cited by 32 publications

(3 citation statements)

References 22 publications

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“…The serum concentration of the different BZD derivatives diazepam, oxazepam, desmethyldiazepam, nitrazepam, flunitrazepam and lorazepam were assayed by gas chromatography with the "electron-capture-detector" technique. The methods used are slightly m d i e d from those originally described by Weinfeld et al (11) and de Silva et al (12).…”

Section: Methodsmentioning

confidence: 99%

The Effect of Flumazenil (Ro 15–1788) in the Management of Self‐induced Benzodiazepine Poisoning

Höjer

Baehrendtz

1988

Journal of Internal Medicine

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Abstract. A double‐blind randomized study was performed to evaluate the efficacy and safety of flumazenil, a benzodiazepine antagonist. The study comprised 52 patients admitted to an intensive care unit because of suspected pure or mixed benzodiazepine poisoning. The degree of consciousness was assessed according to a modified Glasgow Coma Scale (MGCS), graded from 4 to 20, immediately before and at consecutive intervals after an i.v. injection of flumazenil or placebo. If there were no clear signs of arousal within 5 min after the blind injection, an injection of flumazenil was given in open design. Five minutes after the blind administration of active drug the MGCS score was increased by an average of 7.4 (p<0.001) in the flumazenil group. In the placebo group the average MGCS score of 7.8 on admission was not significantly increased by placebo, but 5 min after flumazenil injection it had increased by 7.3 to 15.1 (p<0.001). Patients who had ingested both alcohol and benzodiazepines were aroused as promptly and clearly (MGCS +8.8; p<0.001) as those who had taken benzodiazepines alone (MGCS +8.4; p<0.001). The patients poisoned with a combination of benzodiazepines and other hypnotic drugs responded less, but still highly significantly (MGCS +5.8; p<0.001). Flumazenil was well tolerated and the safety of the antidote seems acceptable. It is concluded that flumazenil can facilitate differential diagnosis and that it is an effective tool in the treatment of drug overdosage when benzodiazepines are involved.

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Section: Methodsmentioning

confidence: 99%

The Effect of Flumazenil (Ro 15–1788) in the Management of Self‐induced Benzodiazepine Poisoning

Höjer

Baehrendtz

1988

Journal of Internal Medicine

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“…Oiazepam (0) and desmethlydiazepam (00) plasma concentrations were determined by the method of Weinfeld et al (1977). using electron capture gas liquid chromatography.…”

Section: Methodsmentioning

confidence: 99%

Diazepam and Desmethyldiazepam Plasma Concentrations in Chronic Anxious Outpatients

Rickels¹,

Wg²,

Rw³

et al. 1984

Pharmacopsychiatry

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Within the framework of a large-scale clinical study on the effect of diazepam in chronic anxiety, diazepam (D) and desmethyldiazepam (DD) plasma concentrations were determined frequently. Significant relationships were found between the clinical effect and the plasma concentrations of D and DD, respectively; a curvilinear relationship resulted if the dosage was disregarded, but within the individual dosage groups the relationship was found to be linear. For these computations, the daily diazepam dose was treated as a covariable in a factorial analysis of variance approach. It was found, in addition, that the daily diazepam dose was one of the most significant predictors of the plasma concentration of D or DD, respectively. The steady state plasma concentrations were highest in patients experiencing an exacerbation of their conditions of anxiety if they were returned to placebo after 14 to 22 weeks of diazepam medication. The lowest steady state concentrations were found with those patients who showed withdrawal symptoms under these conditions.

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“…Patients-105 Unconscious adults admitted consecutively with suspected drug overdosage during 18 months from a total of 362 cases of poisoning. Exclusion criteria were pregnancy, epilepsy, obvious poisoning with drugs identified unequivocally from information from relatives or others as other than benzodiazepines, and coma score >10 on a scale graded from 4 to 20.…”

mentioning

confidence: 99%

Diagnostic utility of flumazenil in coma with suspected poisoning: a double blind, randomised controlled study.

Höjer

Baehrendtz

Matell

et al. 1990

BMJ

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Objective-To assess the diagnostic value and safety of the benzodiazepine antagonist flumazenil in patients with coma ofunclear origin with suspected poisoning.Design-Double blind, placebo controlled, randomised study.Setting-Intensive care unit at a major teaching hospital.Patients-105 Unconscious adults admitted consecutively with suspected drug overdosage during 18 months from a total of 362 cases of poisoning. Exclusion criteria were pregnancy, epilepsy, obvious poisoning with drugs identified unequivocally from information from relatives or others as other than benzodiazepines, and coma score >10 on a scale graded from 4 to 20. Patients were allocated randomly to receive flumazenil (21 men and 32 women) or placebo (25 men and 27 women).Interventions -Intravenous injection offlumazenil (10 ml, 0-1 mg/ml) or placebo (10 ml vehicle alone) given double blind over three minutes.Main outcome measures -Serum and urine concentrations ofbenzodiazepines, antidepressants, and several other agents; blood gas tensions; standardised evaluation on admission and five minutes after the injection by means of coma scale score and urgent diagnostic or therapeutic interventions indicated according to the history and clinical examination; standardised interview after the injection to try to ascertain further information; and adverse reactions.Results-Benzodiazepines were found in the serum in 36 of the 53 patients in the flumazenil group and in 37 of the 52 who received placebo. The average coma scale score increased significantly after injection in the flumazenil group (6-4 v 12-1, p<0-001) but not in the placebo group. In the flumazenil group several interventions were rendered unnecessary by the injection: gastric lavage and urinary catheterisation (19 patients each), intubation (21), artificial ventilation and computed tomography of the brain (three patients each), blood culture and lumbar puncture (one patient each), and electroencephalography (two). In the placebo group the indications for these procedures did not change in any patient after injection. The 95% confidence interval for the difference in reduction of the frequency ofindications for gastric lavage after injection between the two groups was 21% to 51%, that for intubation 25% to 55%, and that for urinary catheterisation 21% to 51%. In the flumazenil group 21 patients gave valuable information on their drug ingestion within 10 minutes after injection compared with only one in the placebo group (p<0-001). Nine adverse reactions were recorded in the flumazenil group, eight of which were graded as mild and one severe.

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Rapid determination of diazepam and nordiazepam in plasma by electron capture gas—liquid chromatography

Cited by 32 publications

References 22 publications

The Effect of Flumazenil (Ro 15–1788) in the Management of Self‐induced Benzodiazepine Poisoning

The Effect of Flumazenil (Ro 15–1788) in the Management of Self‐induced Benzodiazepine Poisoning

Diazepam and Desmethyldiazepam Plasma Concentrations in Chronic Anxious Outpatients

Diagnostic utility of flumazenil in coma with suspected poisoning: a double blind, randomised controlled study.

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