A radioimmunoassay for nortriptyline (and other tricyclic antidepressants) in plasma.

1978 ◽  
Vol 24 (4) ◽  
pp. 549-554 ◽  
Author(s):  
K P Maguire ◽  
G D Burrows ◽  
T R Norman ◽  
B A Scoggins
Keyword(s):  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Cross Reactivity ◽  
Tricyclic Antidepressant ◽  
Major Metabolite ◽  
Plasma Samples ◽  
Dilution Technique ◽  
Concurrent Use ◽  
Set Up ◽  
Double Isotope

Abstract The radioimmunoassay for nortriptyline described here can detect as little 1 microgram/liter of plasma. Within-day precision and day-to-day precision (CV) were +/- 6 and +/- 11%, respectively, over the concentration range 100-200 microgram/liter. The major metabolite hydroxy-nortriptyline, does not cross react with the antiserum. Results so obtained correlate closely with results by a double-isotope derivative dilution technique. The major advantages of this technique over currently available methods are its sensitivity, convenience (many samples can be processed in one day), simplicity, and cost. Further, prior extraction of plasma samples is not required. Cross-reactivity studies have been carried out with all other available tricyclic antidepressants. The antiserum has the ability to bind these drugs, thus radioimmunoassay for all the tricyclic antidepressant drugs can be set up because concurrent use of more than one of these drugs is rare.

Quetiapine Cross-Reactivity with Plasma Tricyclic Antidepressant Immunoassays

2005 ◽  
Vol 39 (9) ◽  
pp. 1446-1449 ◽  
Author(s):  
E Martin Caravati ◽  
JoEtta M Juenke ◽  
Barbara I Crouch ◽  
Kathleen T Anderson
Keyword(s):  
Tricyclic Antidepressants ◽  
Antipsychotic Agent ◽  
Structural Similarity ◽  
Cross Reactivity ◽  
Tricyclic Antidepressant ◽  
Spiked Plasma ◽  
Screening Assays ◽  
Drug Free ◽  
Spiked Plasma Sample

BACKGROUND: Toxicology screens obtained on patients who have overdosed on drugs frequently include tricyclic antidepressants (TCAs) as part of the evaluation. Quetiapine is an antipsychotic agent with structural similarity to the TCAs. OBJECTIVE: To determine whether quetiapine may cross-react with plasma TCA immunoassays in vitro using commonly available autoanalyzers. METHODS: Quetiapine stock solution was added to 9 separate samples of pooled drug-free human plasma to produce concentrations ranging from 1 to 640 ng/mL that were verified by gas chromatography. No quetiapine metabolites were present. Each spiked plasma sample was tested in a blinded fashion using the Abbott Tricyclic Antidepressant TDx Assay on the TDxFLx autoanalyzer in 2 separate laboratories, the Syva Emit tox Serum Tricyclic Antidepressant Assay on the AU400 autoanalyzer and the S TAD Serum Tricyclic Antidepressant Screen on the ACA-Star 300 autoanalyzer. The TDx assay is quantitative, while Emit and S TAD are qualitative screening assays with a threshold of 300 ng/mL for TCA positivity. The outcome of interest was a positive TCA result. RESULTS: The quantitative assay showed concentration-related TCA cross-reactivity beginning at quetiapine concentrations of 5 ng/mL. The 640-ng/mL spiked sample produced TCA results of 379 and 385 ng/mL in labs 1 and 2, respectively. The qualitative assays were screened as TCA positive at quetiapine concentrations of 160 and 320 ng/mL for the S TAD and Emit assays, respectively. CONCLUSIONS: Quetiapine cross-reacts with quantitative and qualitative plasma TCA immunoassays in a concentration-dependent fashion. Therapeutic use or overdose of quetiapine may result in a false-positive TCA immunoassay result.

Column deactivation in analysis for underivatized tricyclic antidepressants by gas chromatography with use of a nitrogen detector.

1983 ◽  
Vol 29 (3) ◽  
pp. 452-455 ◽  
Author(s):  
B Vinet
Keyword(s):  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Glass Tube ◽  
Solid Support ◽  
Tricyclic Antidepressant ◽  
Low Flow ◽  
Sensitive Detector ◽  
Linear Calibration ◽  
Deactivation Process ◽  
Nanogram Level

Abstract I describe deactivation treatment of the OV-17 chromatographic column to minimize adsorption of tricyclic antidepressant drugs on the solid support of the column. The procedure involves heat treatment at 399 degrees C under a low flow of nitrogen, with bleeding of OV-17 liquid phase from the injector tube into the column. The column is then conditioned with vapors of phenyldiethanolamine succinate, added to the carrier gas stream by bleeding from a coated injector glass tube. This deactivation process much improves the chromatographic performance of the column, allowing a sensitivity at the nanogram level with a nitrogen-sensitive detector. Determinations of tricyclic antidepressants in plasma with such a deactivated column results in a low CV and a linear calibration curve, reflecting the effectiveness of the deactivation.

Therapeutic drug monitoring of non-tricyclic antidepressant drugs

2004 ◽  
Vol 42 (11) ◽  
Author(s):  
Philip B. Mitchell
Keyword(s):  
Therapeutic Drug Monitoring ◽  
Drug Monitoring ◽  
Selective Serotonin Reuptake Inhibitors ◽  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Tricyclic Antidepressant ◽  
Therapeutic Drug ◽  
Cytochrome P450 Enzymes ◽  
Clinical Value ◽  
Major Benefit

AbstractTherapeutic drug monitoring (TDM) of many of the tricyclic antidepressants (TCAs) has been demonstrated to be of clear clinical value. This article reviews studies of TDM for the selective serotonin reuptake inhibitors (SSRIs) and other non-tricyclic antidepressants such as venlafaxine, nefazodone, trazodone, mianserin and bupropion. No definitive therapeutic concentrations have been demonstrated for these agents, nor have levels indicative of toxicity been reported. The major benefit of TDM for these agents would appear to be in the assessment of the apparently treatment-refractory depressed patient, to determine whether such lack of response is related to inadequate levels that would suggest either poor compliance, ultra-rapid metabolism, or drug interactions leading to induction of metabolising enzymes. Potential future applications of TDM, in conjunction with genotyping of cytochrome P450 enzymes and pharmacogenomic evaluations, are discussed.

On the Slowness of Action of Tricyclic Antidepressant Drugs

1972 ◽  
Vol 120 (559) ◽  
pp. 673-677 ◽  
Author(s):  
Ian Oswald ◽  
Vlasta Brezinova ◽  
D. L. F. Dunleavy
Keyword(s):  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Tricyclic Antidepressant ◽  
Tricyclic Antidepressant Drugs

It is widely believed that tricyclic antidepressants such as imipramine bring little benefit for ten days, that three or four weeks are needed to be sure, and that five or six weeks are needed to get the patient really back to health. Why should it take so long? Is it even true? If true it seems remarkable that such a challenge should have been largely ignored by theorists content to rest their arguments upon acute experiments with animals.

scholarly journals Lipoxygenase-Mediated N-Demethylation of Imipramine and Related Tricyclic Antidepressants in the Presence of Hydrogen Peroxide

1999 ◽  
Vol 18 (4) ◽  
pp. 251-257 ◽  
Author(s):  
Jianan Hu ◽  
Mini Sajan ◽  
Arun P. Kulkarni
Keyword(s):  
Hydrogen Peroxide ◽  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Nordihydroguaiaretic Acid ◽  
Tricyclic Antidepressant ◽  
Butylated Hydroxytoluene ◽  
Radical Intermediate ◽  
Free Radical Intermediate ◽  
First Time ◽  
Assay Conditions

In this study, we examined the ability of soybean lipoxygenase to mediate the N-demethylation of imipramine and related drugs in the presence of hydrogen peroxide. Formaldehyde generation resulting from the N-demethylation of imipramine, a prototype drug, was found to depend on incubation time, and the concentration of the enzyme, imipramine, and hydrogen peroxide. Under optimal assay conditions, Vmax values of 14 to 18 nmol formaldehyde/min/nmol enzyme or 133 to 164 nmol formaldehyde/min/mg protein were observed. An inhibition of formaldehyde and desipramine formation by nordihydroguaiaretic acid confirmed the lipoxygenase involvement. The blockade of the reaction by glutathione, dithiothreitol, butylated hydroxyanisole (BHA), and butylated hydroxytoluene (BHT) indicated the generation of a free radical intermediate from imipramine. Desipramine, trimipramine, clomipramine, and diltiazem, but not amitriptyline and doxepin, were also oxidized, albeit at a lower rate. Collectively, the evidence gathered in this study suggests, for the first time, that tricyclic antidepressant drugs may undergo lipoxygenase-catalyzed N-demethylation.

scholarly journals Development of Sodium Sulfate Induced Water Based Dispersive Liquid–Liquid Microextraction for the Extraction of Four Tricyclic Antidepressants in Urine Samples Prior to Their Determination by Gas Chromatography–Mass Spectrometry

2020 ◽  
Vol 27 (1) ◽  
pp. 76-85
Author(s):  
Ali Mohebi ◽  
Mir Ali Farajzadeh ◽  
Abolghasem Jouyban ◽  
Mahboob Nemati ◽  
Mohammad Reza Afshar Mogaddam
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
Tricyclic Antidepressant ◽  
Urine Samples ◽  
Gas Chromatography Mass Spectrometry ◽  
Tricyclic Antidepressant Drugs ◽  
Dispersive Liquid Liquid Microextraction ◽  
Liquid Microextraction

Background: Because of the narrow therapeutic range of tricyclic antidepressant drugs, their determination in biological samples is of great importance. In this work, a fast and environment friendly sample pretreatment method based on a dispersive liquid–liquid microextraction was developed for the extraction and preconcentration of four tricyclic antidepressants including nortriptyline, amitriptyline, desipramine, and clomipramine in urine prior to their determinations by gas chromatography–mass spectrometry. Methods: In the suggested method, an appropriate mixture of Na2SO4 solution (as phase separation agent and disperser) containing isopropanol (extraction solvent) is rapidly injected into an alkaline aqueous sample solution containing Na2SO4 and the analytes. As a result, a cloudy mixture is formed and the tiny droplets of the extractant containing the extracted analytes are collected on the surface of the aqueous phase after centrifuging. Finally, an aliquot of the collected organic phase is removed and injected into the separation system for the quantitative analysis. Results: Under the optimum conditions, the enrichment factors and extraction recoveries were in the ranges of 380–440 and 76–88%, respectively. The limits of detection and quantification were obtained in the ranges of 11–24, and 41–75 ng/L, respectively. The relative standard deviations of the proposed method were ≤ 6.1% for intra– (n=6) and inter–day (n=4) precisions at a concentration of 100 ng/L of each analyte. Conclusion: The introduced method was satisfactorily utilized for the simultaneous determination of the selected tricyclic antidepressant drugs in the patient’s urine samples.

Cardiac Effects of Different Tricyclic Antidepressant Drugs

1976 ◽  
Vol 129 (4) ◽  
pp. 335-341 ◽  
Author(s):  
G. D. Burrows ◽  
J. Vohra ◽  
D. Hunt ◽  
J. G. Sloman ◽  
B. A. Scoggins ◽  
...  
Keyword(s):  
Tricyclic Antidepressants ◽  
Animal Experiments ◽  
Antidepressant Drugs ◽  
Clinical Findings ◽  
Tricyclic Antidepressant ◽  
Atrioventricular Conduction ◽  
Clinical Implications ◽  
Cardiac Effects ◽  
Tricyclic Antidepressant Drugs ◽  
Therapeutic Doses

SummaryThe effects of tricyclic antidepressants on the heart are reviewed. Statistically significant increases in heart rate and in atrioventricular conduction times were found following the administration of tricyclic drugs to 32 depressed patients. The method of His bundle electrocardiography was used to study atrioventricular conduction in ambulant patients and in patients admitted after an overdose of tricyclic antidepressant drugs. Distal conduction defects were frequently found in patients following tricyclic overdosage, but these were not seen with doxepin overdosage. Impaired distal conduction was also found in occasional patients on therapeutic doses of tricyclic drugs. Some animal experiments giving similar results to the above clinical findings are also described. The clinical implications of these findings are discussed.

TWO CURRENT POISONINGS: TRICYCLIC DRUGS AND METHADONE

PEDIATRICS ◽  
1973 ◽  
Vol 51 (5) ◽  
pp. 919-922
Author(s):  
Jay M. Arena
Keyword(s):  
Tricyclic Antidepressants ◽  
Antidepressant Drugs ◽  
The United States ◽  
Tricyclic Antidepressant ◽  
Muscle Rigidity ◽  
Conduction Disturbances ◽  
Tricyclic Compounds ◽  
Ectopic Beats ◽  
Ventricular Tachycardias ◽  
Wide Usage

One of the most serious types of poisoning, occurring with increasing frequency in children as well as in adults in the United States, arises from the wide usage and increased accessibility of antidepressant drugs, specifically the tricyclic compounds. These include imipramine (Tofranil), desipramine (Norpramin, Pertofrane), amitriptyline (Elavil), nortriptyline (Aventyl), protriptyline (Vivactyl), trimipramine (Surmontil), and opipramol. Doxepin hydrochloride, a dibenzoxepin compound, is structured similarly to amitriptyline except for the replacement of one carbon atom by an oxygen atom in the tncyclic ring. There have been a number of serious cardiac arrhythmias, conduction disturbances, and heart blocks associated with intoxications from tricyclic antidepressant tranquilizers. The most commonly seen disturbances of cardiac function from overdoses of these drugs are supraventricular tachycardia, widening of the QRS complexes, depression of the S-T segments, and abnormal T waves. Disturbances of rhythm and conduction which have been reported include atrial and ventricular tachycardias, flutters, and fibrillations, wandering pacemaker, multifocal extrasystoles (ectopic beats), complete or partial atrioventricular and intraventricular blocks, and cardiac arrest. In addition to the cardiac disturbances, intoxication with tricyclic antidepressants also produces the peripheral signs of atropinism and symptoms of vomiting, thirst, drowsiness or dizziness, and signs of mydriasis, nystagmus, agitation or stupor, bowel and bladder paralysis, muscle rigidity, tremors, hyperreflexia, athetoid or clonic movements, convulsions, hypertension or hypotension, depressed respiration, cyanosis, hyperthermia or hypothermia, and coma. The most serious phase appears to be the first 12 hours, but during recovery a deep lethargy may alternate with tremors, agitation, delirium, hallucinations, mental confusion, and persistent insomnia.

Rapid radioisotopic procedure for determination of nortriptyline in plasma.

1976 ◽  
Vol 22 (6) ◽  
pp. 761-764 ◽  
Author(s):  
K P Maguire ◽  
G D Burrows ◽  
J P Coghlan ◽  
B A Scoggins
Keyword(s):  
Therapeutic Response ◽  
Antidepressant Drugs ◽  
Tricyclic Antidepressant ◽  
A Value ◽  
Drug Concentrations ◽  
The Mean ◽  
The Relationship ◽  
Mean Concentration ◽  
Double Isotope

Abstract With the widespread use of tricyclic antidepressant drugs, the relationship between the concentration of the drug in the plasma and the therapeutic response is of considerable interest. We describe a double-isotope derivative dilution procedure for measuring plasma nortriptyline. In the method, [14C]nortriptyline is used for estimating procedural losses and [3H]acetic anhydride for derivative formation. The assay is rapid and adequately specific, sensitive, precies, and reproducible for routine clinical use. We used it to investigate the variation in steady-state drug concentrations in plasma of persons who were on a 150 mg/day dose of nortriptyline. Intra-individual variation from day to day was 10-14%. This variation was not significantly affected by the dosage schedule, the time of sampling after an oral dose, or the storage of the plasma samples. For 19 patients on 150 mg of nortriptyline per day, the mean concentration in plasma was 181 +/- 22 (SE) mug/liter, a value that compares well with our previous findings and those of other groups.

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