Geoffrey W. Peng

Method for the rapid estimation of the total body drug clearance and adjustment of dosage regimens in patients during a constant-rate intravenous infusion

A simple method is proposed to estimate the total body clearance and biological half-life of drugs in patients by determining two blood or plasma levels of drugs separated by an appropriate interval during the constant-rate intravenous infusion. The method is based on the assumptions that the drug disposition in the body can be adequately described by the linear onecompartment open model and its apparent volume of distribution can be estimated with a reasonable degree of accuracy from the literature data. The validity of this newly proposed method was demonstrated in three rabbits using theophylline as a test drug. Results of theoretical error analyses indicate that the method is potentially useful in providing an early guide for dosing adjustments for those potent drugs whose elimination rates have been shown to vary greatly in patients. The method may be particularly useful in patients with changing elimination kinetics of drugs. Effects of the accuracy in Vdestimate, plasma level assay, and sampling time interval on the error of total body clearance estimation are discussed.

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.

High-pressure liquid chromatographic assay of netilmicin in plasma.

A high-pressure liquid chromatographic method for the quantitative determination of netilmicin in plasma was developed. The procedures involve acetonitrile protein precipitation, methylene chloride extraction, and dansylation to form the fluorescent dansyl derivative of netilmicin, which is extracted into ethyl acetate and chromatographed on a reverse-phase column with aqueous acetonitrile as the mobile phase. A good linear relationship between peak height measurements and netilmicin concentrations was found. This method is sensitive and reproducible; a netilmicin concentration as low as 0.5 μg/ml can be measured with only 0.1 ml of plasma sample. The results of assays of plasma or serum samples by this high-pressure liquid chromatographic method correlate well with those obtained by microbiological assays.

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.

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.

Comparison of gentamicin C1 and (C1a, C2)-levels in patients

SummaryA high performance liquid chromatographic (HPLC) assay method has been used to measure gentamicin serum concentrations in patients receiving gentamicin complex. The HPLC method resolves gentamicin C1 from the other two components, C1a and C2; gentamicin C1a and C2 cochromatograph. In the analysis of 46 serum samples collected from 16 patients it was found that the mean ratio (PHR) of the peak height of gentamicin C1 to the height of the peak due to components C1a and C2 was 0.53±0.05; this value agreed well with the PHRs usually found from the HPLC analysis of aqueous solutions of gentamicin complex or of gentamicin dosage forms. In an additional two patients, the HPLC analysis of a sample of the gentamicin dosage form administered, a urine sample, and serum samples, resulted in almost identical PHRs for the respective patients. Finally, similar results were obtained from an experiment in a rabbit. It was concluded that the disposition of all three components of gentamicin complex are the same or very similar.