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Biomedical subjects

R L Nation

Publications and source records attributed to R L Nation.

At least 91 records · Page 5Linked to original sources

Simultaneous determination of betamethasone, betamethasone acetate and hydrocortisone in biological fluids using high-performance liquid chromatography.

A sensitive, specific, reproducible and rapid high-performance liquid chromatographic method for the simultaneous quantitation of betamethasone, betamethasone 21-acetate and hydrocortisone in biological fluids is described. Hydrocortisone acetate is used as an internal standard and the samples are extracted with dichloromethane before chromatographing on a reversed-phase system. Detection at two ultraviolet wavelengths (254 nm and 240 nm) was used to assess the specificity of the system, and the sensitivity was found to be greater than 10 ng for all steroids. The speed with which this assay can be performed makes it particularly useful for pharmacokinetic studies, and plasma concentration--time profiles resulting from the administration of betamethasone phosphate and betamethasone acetate are presented.

Betamethasone↗

Simultaneous quantitation of chlormethiazole and two of its metabolites in blood and plasma by gas--liquid chromatography.

A simple and rapid gas chromatographic method for the quantitation of chlormethiazole and two of its pharmacologically active metabolites, 5-acetyl-4-methylthiazole and 5-(1-hydroxyethyl)-4-methylthiazole, in plasma and blood is described. The total analysis time is less than 20 min for a single sample. The method requires 50--500 microliter of plasma or 1 ml of blood. The compounds are detected with a nitrogen--phosphorus detector. An internal standard technique is used for the quantitation. Calibration data are linear over the range 32--2376 ng of chlormethiazole and a similar range of the metabolites in plasma. The method may be used for pharmacokinetic studies.

Adult↗

Sorption of chlormethiazole by intravenous infusion giving sets.

The sorption of chlormethiazole by intravenous infusion giving sets was investigated. Average recoveries of chlormethiazole following 500 ml infusions were 78.5%, 82.2% and 71.2% for the IVAC Volume Infusion Set, Travenol Code AHC 2890 Blood Administration Set and the McGaw Metriset, respectively. The effluent concentration-time profile using set up procedures and infusion rates similar to those used clinically were followed. When compared to solutions flowing at an infusion rate of 75 and 150 ml/h, loss of chlormethiazole from solutions standing static in the infusion sets was higher while that of solutions flowing at a high rate of 999 ml/h was lower. The clinical and pharmacokinetic significance of these phenomena are discussed.

Adsorption↗

The placental transfer of betamethasone.

The plasma concentrations of betamethasone in a maternal peripheral vein (mv) and in the umbilical vein (uv) were measured at delivery in eleven patients after the administration of betamethasone phosphate equivalent to 8 mg betamethasone. Betamethasone concentrations were measured in plasma using a specific and sensitive HPLC assay. The time interval between the last dose and delivery ranged from 56 min to 800 min and over this time period the mean plasma concentration ratio Cuv/Cmv was 0.28 +/- 0.04 (SD) and exhibited no time dependence.

Adult↗

Design of infusion regimens to achieve and maintain a predetermined plasma drug level range.

A method is proposed for the design of dosage regimens using two consecutive constant-rate intravenous infusions to rapidly achieve and maintain plasma drug levels within a predetermined range. By this method, the plasma level will rise to a predetermined maximum at the end of the loading infusion, decrease rapidly to a chosen fraction of the ultimate steady-state level, and then slowly rise to the steady-state level. The method may be particularly useful for drugs exhibiting extensive "multi-compartment" kinetics. Compared with other methods, this approach allows either or both a shorter loading infusion and a lower peak plasma level. Application of this method to clomethiazole therapy for the sedation of pregnant women at term is also discussed.

Anticonvulsants↗

Chlorpheniramine. I. Rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine by high-performance liquid chromatography.

A method was developed for the rapid quantitative analysis of chlorpheniramine in plasma, saliva and urine using high-performance liquid chromatography. A diethyl ether or hexane extract of the alkalinized biological samples was extracted with dilute acid which was chromatographed on a reversed-phase column using mixtures of acetonitrile and ammonium phosphate buffer as the mobile phase. Ultraviolet absorption at 254 nm was monitored for the detection and brompheniramine was employed as the internal standard for the quantitation. The effects of buffer, pH, and acetonitrile concentration in the mobile phase on the chromatographic separation were investigated. A mobile phase 20% acetonitrile in 0.0075 M phosphate buffer at a flow-rate of 2 ml/min was used for the assays of plasma and saliva samples. A similar mobile phase was used for urine samples. The drug and internal standard were eluted at retention volumes of less than 17 ml. The method can also be used to quantify two metabolites, didesmethyl- and desmethylchlorpheniramine, in the urine. The method can accurately measure chlorpheniramine levels down to 2 ng/ml in plasma or saliva using 1 ml of sample, and should be adequate for biopharmaceutical and pharmacokinetic studies. Various precautions for using the assay are discussed.

Chlorpheniramine↗

Plasma concentrations of propranolol and 4-hydroxypropranolol during chronic oral propranolol therapy.

1 The plasma levels of propranolol and 4-hydroxypropranolol have been measured in 17 hypertensive patients receiving chronic oral therapy with propranolol. 2 The range of plasma propranolol concentrations was from 5.3 to 300 ng/ml, and that of 4-hydroxypropranolol was from 2.1 to 36.0 ng/ml. 3 The mean (+/- s.d.) plasma concentration ratio of 4-hydroxypropranolol to propranolol was 0.130 (+/- 0.005); however, a very wide range was observed with individual values ranging from 0.057 to 0.241. 4 A statistically significant correlation was observed between the plasma concentration of 4-hydroxypropranolol and that of propranolol. 5 Propranolol and 4-hydroxypropranolol plasma concentrations were each significantly, but poorly, correlated with daily propranolol dose. 6 The clinical significance of the results has been discussed.

Adult↗

Simple, rapid and micro high-pressure liquid chromatographic method for the simultaneous determination of tolbutamide and carboxy tolbutamide in plasma.

A rapid high-pressure liquid chromatographic (HPLC) assay is described for the quantitative analysis of tolbutamide and its major metabolite, carboxy tolbutamide in plasma. An aliquot (25--100 microliter) of plasma was prepared for chromatography by deproteinization as follows. One volume of plasma and 2.5 volumes of acetonitrile were vortex mixed for a few seconds and then centrifuged for approx. 1 min. A 50-microliter sample of the clear supernatant was injected into the chromatograph. A mu Bondapak C18 reversed-phase column was used with a mobile phase acetonitrile--0.05% phosphoric acid (45:55) at a flow-rate of 1.5 ml/min. The column effluent was monitored by a variable-wavelength UV detector set at 200 nm. Tolbutamide and its metabolite had retention times of 5.75 and 3.25 min, respectively. The procedure yuelds reproducible results with sensitivity adequate for routine clinical monitoring of plasma levels or for single-dose pharmacokinetic studies. A number of commonly used drugs do not interfere with the method. A single plasma sample can be analyzed in approx. 9 or 10 min.

Animals↗

High-pressure liquid chromatographic method for the simultaneous quantitative analysis of propranolol and 4-hydroxypropranolol in plasma.

A simple and rapid high-pressure liquid chromatographic procedure is reported for the simultaneous quantitative determination of propranolol and 4-hydroxypropranolol in plasma. Following an extraction the samples are chromatographed on a reversed-phase column and the components in the column effluent are detected by fluorescence monitoring. Using 1-ml plasma samples propranolol and 4-hydroxypropranolol concentrations at least as low as 1 ng/ml and 5 ng/ml, respectively, can be quantitated. The reproducibility of the method is satisfactory and no interference from endogenous plasma components or other drugs has been observed. A single plasma sample can be analyzed in approximately 20 min.

Chromatography, High Pressure Liquid↗

Simple, rapid, and micro high-pressure liquid chromatographic determination of plasma griseofulvin levels.

A rapid high-pressure liquid chromatographic assay is described for the quantitative determination of griseofulvin in plasma. An aliquot (25--10 microliter) of plasma was deproteinized by a simple procedure involving the addition of 2.5 volumes of acetonitrile, vortex mixing for a few seconds, and centrifugation for 1 min. The clear supernate, 50 microliter, was injected into the high-pressure liquid chromatograph. A reversed-phase column was used with a mobile phase of distilled water-acetonitrile (1:1) at a flow rate of 2 ml/min and was operated at ambient temperature. A fluorescent detector with an excitation wavelength of 260 nm was employed to monitor the column effluent. Griseofulvin had a retention time of 3.8 min. This procedure yields reproducible results with high sensitivity; plasma concentrations as low as 50 ng/ml can be measured. Several commonly used drugs do not interfere. Analysis of plasma samples collected from a rabbit injected with griseofulvin indicated that the procedure is suitable for pharmacokinetic studies and clinical monitoring of plasma concentrations in patients. Assay turnaround time is less than 6 min. For clinical monitoring of plasma griseofulvin concentrations, a sample volume as small as 10 microliter can be used.

Animals↗

Metabolism and urinary excretion of benzhexol in humans.

1. Benzhexol and three of its metabolites excreted in urine in man have been investigated by g.l.c.--mass spectrometry. 2. Three isomeric hydroxylated metabolites were identified as the 1-(hydroxycyclohexyl)-1-phenyl-3-piperidinopropan-1-ols. 3. The amounts of benzhexol and its identified metabolites have been semiquantitatively determined after a single oral dose in two healthy adults. Approx. 56% of the dose was excreted as the hydroxylated metabolites. The levels of benzhexol excreted were too low to be measured by the techniques used.

Adult↗

Lignocaine kinetics in cardiac patients and aged subjects.

1 The pharmacokinetics following long term intravenous infusion of lignocaine to cardiac patients have been examined. 2 Plasma levels and half-lives of lignocaine and monoethylglycinexylidide (MEGX) showed wide inter-patient variability. 3 Toxicity reactions to therapy were associated with elevated lignocaine and/or MEGX plasma levels. 4 In a separate study the effect of age on the pharmacokinetics of lignocaine was examined using bolus doses (50 mg) of the drug to young and aged subjects. 5 Elderly subjects had significantly longer half-lives for lignocaine compared to younger individuals although no change in plasma clearance occurred. 6 The drug appeared to distribute differently in the aged as reflected by significantly increased apparent volumes of distribution. 7 The 24 h urinary recovery of the major metabolite (total 4-hydroxyxylidine) showed a significant reduction in the elderly when compared to the young. 8 The clinical significance of these studies with respect to lignocaine therapy has been discussed.

Adult↗