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Biomedical subjects

R N Gupta

Publications and source records attributed to R N Gupta.

At least 37 records · Page 2Linked to original sources

Concentration response relationships of amiodarone and desethylamiodarone.

Twelve patients with frequent ventricular premature depolarizations (VPDs) received amiodarone, 600 mg/day, for up to 8 weeks. On days 0, 1, 4, 8, 15, 22, 36, and 57 of treatment, 24-hour ambulatory ECGs were obtained, and multiple blood samples were taken for determination of amiodarone and desethylamiodarone plasma concentrations. All patients had at least 75% suppression of VPDs. The mean duration of therapy before the onset of antiarrhythmic effect was 13.2 days (range 1 to 36 days). Trough amiodarone and desethylamiodarone plasma concentrations at the time of onset of antiarrhythmic effect were 0.86 +/- 0.48 mg/L and 0.23 +/- 0.15 mg/L, respectively. Sixty-seven percent of patients responded at amiodarone concentrations below 1.0 mg/L. For each patient there was a progressive decrease in frequency of VPDs as both amiodarone and desethylamiodarone concentrations increased. Regression modeling indicated that both amiodarone and desethylamiodarone plasma concentrations explained significant variability in the frequency of VPDs, and amiodarone and desethylamiodarone plasma concentrations were highly correlated with each other. There was a trend for desethylamiodarone to explain more variability in frequency of VPDs than amiodarone.

Amiodarone↗

Determination of unconjugated 3-methoxy-4-hydroxyphenylglycol by liquid chromatography for monitoring inhibition of monoamine oxidase activity in plasma.

We describe a simple method for extracting 3-methoxy-4-hydroxyphenylglycol (MHPG) from plasma. The sample is applied to a 1-mL "Extrelut" column (EM Industries) and eluted 15 min later with ethyl acetate. After mixing the eluate with pentane and back-extraction into water, we inject 25 or 50 microL of the aqueous phase onto a Beckman 15 cm x 4.6 mm (i.d.) column packed with 5-micron ODS particles (Beckman). Peaks are detected with a coulometric detector. The resulting chromatogram is clean, with few extraneous peaks. The extraction recovery of MHPG is 55-60%, which allows for detection of as little as 0.2 microgram of the analyte per liter. The decrease in the concentration of MHPG in plasma of patients treated with phenelzine agrees with the decrease in monoamine oxidase activity in platelets of these patients.

Blood Platelets↗

Liquid chromatographic determination of mexiletine and tocainide in human plasma with fluorescence detection after reaction with a modified o-phthalaldehyde reagent.

A liquid chromatographic procedure for the determination of mexiletine or tocainide in human plasma is described. Plasma, after the addition of a homologue of mexiletine or of tocainide, is extracted with dichloromethane. The extract is evaporated and reconstituted in a non-aqueous o-phthalaldehyde--mercaptoethanol reagent. An aliquot of the solution is chromatographed on a reversed-phase Ultrasphere-octyl column. The peaks are detected by fluorescence (lambda ex = 350 nm and lambda em = 445 nm). The fluorescent derivatives of the drugs and internal standards are stable at room temperature and give symmetrical single peaks. Use of fluorescamine as a reagent to prepare fluorescent derivatives of mexiletine and tocainide prior to chromatography is also evaluated.

Chromatography, Liquid↗

Liquid chromatographic determination of inhibition of monoamine oxidase activity in platelet rich plasma of depressed patients treated with phenelzine.

Monitoring platelet monoamine oxidase activity in plasma of depressed patients receiving monoamine oxidase inhibitors is used as an indicator of therapeutic dosage and efficacy. In this study enzyme activity in platelets vs platelet rich plasma was compared. An aliquot of platelet rich plasma (PRP) was incubated with 4-hydroxy-3-methoxy-benzylamine as substrate. After stopping the enzymatic reaction, m-hydroxybenzaldehyde was added to the mixture as internal standard. The reaction mixture was extracted with toluene to isolate vanillin, the deamination product of the substrate, and the internal standard. The toluene layer was collected and back extracted into dilute tetramethylammonium hydroxide. An aliquot of the aqueous layer was chromatographed on a non-silica resin base reversed phase column with an alkaline phase. The peaks were detected by an absorbance detector at 350 nm. There was no significant difference in the decrease of monoamine oxidase activity when determined using platelet rich plasma versus washed platelets.

Benzaldehydes↗

Drug level monitoring: sedative hypnotics.

Barbiturates and other traditional non-barbiturate sedative hypnotics are still extensively prescribed for the treatment of insomnia. There are a number of situations where identification or quantitative determination of these agents in biological fluids is required. Gas-chromatography offers highly sensitive and specific procedures for the determination of these compounds. The use of a nitrogen-specific detector allows a relatively simple sample preparation for sensitive detection and the use of capillary columns with bonded liquid phase allows separation of barbiturates without derivatization. In recent years liquid chromatography has also been extensively applied to the determination of these compounds. Sensitivity and selectivity of detection of barbiturates have been improved with the use of an alkaline mobile phase. Immunoassays for the determination of therapeutic concentrations of phenobarbital are very popular as the assays can be rapidly performed automatically. Use of these techniques has been extended for emergency detection of barbiturate overdose and for monitoring high-dose pentobarbital therapy.

Barbiturates↗

Specificity of the combined dexamethasone suppression and TRH/TSH tests in melancholia.

Subjects for this study were 61 acute psychiatric inpatients. Forty two (42) qualified for a RDC diagnosis of Major Depressive Disorder (MDD) and 19 for other disorders. After a 7-10 days drug withdrawal period patients were subjected to the dexamethasone suppression and TRH/TSH tests. TSH was measured using a RIA. Cortisol was measured using a CPB technique. Eighteen (18) of the 42 MDD patients and 1 of the 19 others had an abnormal DST (sensitivity 43%, specificity 94%). Twenty two (22) depressed patients and 4 others had a blunted TSH response (sensitivity 52%, specificity 79%). Thirteen (13) depressives and none of the others had abnormal responses to both tests (sensitivity 31%, specificity 100%). DST nonsuppression alone and blunted TSH response alone were not a function of severity of illness, sex, age of onset, family history or RDC subtype. The 13 MDD patients with the combined neuroendocrine abnormality were more severely depressed, had longer episodes of illness, were older and had a later age of onset of their first episode. Our results add support to the suggestion that serial neuroendocrine challenge studies might be of particular relevance and significance in the diagnosis and management of elderly psychotic depressed patients.

Adolescent↗

Liquid chromatographic determination of urinary metanephrines after pre-column oxidation to vanillin.

Urine after the addition of phenylephrine as internal standard is hydrolyzed and passed through a disposable BondElut SCX column. After washing the column, metanephrines and the internal standard are eluted with dilute ammonia. The eluate is treated with periodate and extracted with toluene. The toluene layer is collected and phenols are extracted into dilute tetramethylammonium hydroxide. An aliquot of the aqueous layer is chromatographed on a nonsilica resin base reversed phase column with an alkaline mobile phase. The peaks are detected by an absorbance detector at 350 nm. There is a baseline separation of vanillin formed by metanephrines and of m-hydroxybenzaldehyde formed by phenylephrine. The procedure is linear from 0.2 mg to 10 mg of metanephrine per liter of urine. The procedure has a high degree of specificity as the commonly prescribed antihypertensive drugs and their metabolites do not interfere.

Benzaldehydes↗

Colorimetric determination of acetaminophen.

A colorimetric procedure for the emergency determination of acetaminophen in plasma is described. Acetaminophen is extracted into ethyl acetate at physiological pH to eliminate salicylate, amino acids and other polar compounds. The extract is treated with Fuller's earth to remove bilirubin and with anhydrous sodium sulphate to remove traces of aqueous droplets containing proteins or uric acid. The extract is back-extracted into carbonate and simultaneously treated with Folin--Ciocalteau reagent to produce a stable colour complex.

Acetaminophen↗

Determination of tricyclic antidepressant drugs by gas chromatography with the use of a capillary column.

A universal gas chromatographic procedure for the determination of the commonly prescribed tricyclic antidepressant drugs in 1 mL of plasma is described. After the addition of internal standards the samples are washed with pentane at acidic pH and extracted with pentane at alkaline pH. The pentane extract is evaporated after the addition of acetic anhydride. Aliquots of a methanolic solution of the residue of evaporated extract are analyzed isothermally on a Durabond 30 m fused silica column. This column is well suited for use with a nitrogen selective detector. The liquid phase is not extracted by repeated injections of methanolic solutions of plasma extracts. When compared to a packed column, this column allows shorter analysis time.

Antidepressive Agents, Tricyclic↗

Liquid-chromatographic determination of nadolol in plasma.

We describe a liquid-chromatographic procedure for determining nadolol in plasma. After an analog of nadolol is added as internal standard, the plasma sample is passed through a disposable BondElut C18 column. After several column washes, nadolol and the internal standard are eluted with methanol, and the eluate is evaporated and reconstituted with the mobile phase (acetonitrile/water, perchloric acid, and tetramethylammonium hydroxide). An aliquot of the extract is chromatographed on a non-silica resin-base reversed-phase column. The peaks are detected by fluorescence (lambda ex = 265 nm and lambda em = 305). Drug and internal standard are well resolved, and only a few extraneous peaks appear. The standard curve ranges from 10 to 400 micrograms/L. We are using this procedure to determine steady-state concentrations of nadolol in patients receiving various dosages of nadolol along with other types of antihypertensive drugs.

Antihypertensive Agents↗

The pharmacokinetics and pharmacodynamics of minaxolone.

Plasma concentrations of minaxolone were measured in 15 female patients during and for up to 3 hours after a minaxolone and nitrous oxide anesthetic. Nine patients received a single dose and six patients two or three doses of minaxolone. Plasma minaxolone decay can be described by two-compartment kinetics. Distribution is rapid, with a mean half-life of 2.1 minutes, and the elimination half-life is short (47 minutes). Plasma clearance is high (1.55 l./min). Plasma levels of minaxolone at recovery were similar in patients receiving both single and multiple doses, suggesting a valid relationship between plasma level and effect. It is suggested that minaxolone may be a suitable agent for administration by continuous infusion.

Adult↗