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J R Miksic

Publications and source records attributed to J R Miksic.

9 recordsLinked to original sources
PubMed1995

Cross-validation of bioanalytical methods between laboratories.

Increased reliance on pharmacokinetic studies in regulatory submissions emphasizes the need for cross-validating bioanalytical methods between different laboratories to allow comparison of data. Globalization of pharmaceutical development results in a greater need to define cross-validation standards. A strategy for performing cross-validation experiments using prepared biological samples of known concentration and "real" samples from clinical trials is presented. The statistical techniques used to compare data sets and establish acceptability of the assays are illustrated by practical examples.

Chemistry Techniques, Analytical↗
PubMed1991

Influence of the mobile phase on salmon calcitonin analysis by reversed-phase liquid chromatography.

The retention properties of calcitonins on a reversed-phase column are examined using salmon calcitonin as the model compound. The effect of the concentration of organic modifier, buffer strength, pH of the mobile phase, and ion-pair reagent are studied. In the absence of an ionic modifier in the eluent the calcitonin peak shapes are not symmetrical. The addition of 0.1% trifluoroacetic acid (TFA), however, results in good peak characteristics without the need to add nonvolatile salts. The retention of the calcitonins was found to be very sensitive to the concentration of the organic modifier (acetonitrile) present in the mobile phase. A change of pH between 2 and 5 has only a slight effect of the k' of salmon calcitonin, but the k' increases significantly at higher pH values. The addition of a phosphate buffer to the mobile phase and an increase in the buffer concentration (0-0.2 M) causes a decrease in the retention of salmon calcitonin. Evidence shows that reproducible, quantitatively measurable data can be obtained using reversed-phase chromatography if the ion-pairing reagent and organic modifier concentrations are carefully controlled. The system also shows a good selectivity for the calcitonin series. Therefore, both highly selective methods (qualitative) as well as quantitative methods for analytical, pharmaceutical, and manufacturing use can be developed by adjusting the high-performance liquid chromatography (HPLC) conditions as discussed.

Amino Acid Sequence↗
PubMed1988

Determination of a new inotropic agent in human plasma by high-performance liquid chromatography.

A new orally active inotropic agent, 6-[3,4-dihydro-3-methyl-(2H)-2-oxoquinozolinyl)]-4,5-dihydro-3- (2H)-pyridazinone (I), is currently under investigation. In support of clinical studies, a HPLC assay for the analysis of compound I in human plasma has been developed. The method involved a solid-phase extraction using C18 cartridge columns washed with methanol-water (20:80) and eluted with acetonitrile-water (70:30). The eluate was then extracted with dichloromethane. A reversed-phase alkylphenyl-bonded column was used as the analytical column. The mobile phase was a mixture of methanol, acetonitrile, 2-propanol and phosphate buffer (pH 4.6). A wavelength of 311 nm was used for detection. The limit of detection of the assay was 2 ng/ml, and the limit of quantitation was 5 ng/ml. A linear calibration range of 5 ng/ml to 1200 ng/ml was obtained with a correlation coefficient less than 0.99. The precision and accuracy were evaluated by analyzing samples of three different concentrations (n = 5), 40, 200 and 800 ng/ml in plasma. The coefficients of variation and the differences from nominal values were less than 10%. The average recovery for 5, 50 and 100 ng/ml of analyte in plasma was about 90%. This assay has been applied to clinical studies with satisfactory performance and to plasma of different species in preclinical studies.

Cardiotonic Agents↗
PubMed1988

Analysis of a new H2 receptor antagonist, 3-amino-5-[3-[4-(1-piperidinoindanyloxy)]propylamino]-1-methyl-1 H-1,2,4-triazole, in human plasma and urine by high-performance liquid chromatography.

A high-performance liquid chromatographic (HPLC) method for the determination of a new H2 receptor antagonist, 3-amino-5-[3-[4-(piperidinoindanyloxy)]propylamino] -1-methyl-1H-1,2,4-triazole (I), in human plasma and urine was developed. The method employs liquid-liquid extraction of the analyte and an internal standard and chromatographic separation using an alkylphenyl-bonded HPLC column. The total time of chromatography was less than 10 min. Sensitivity was 10 ng/ml for the plasma analysis and 1 microgram/ml for the analysis of I from urine. The coefficients of variation, based on interpolated concentrations, were less than 10%. The method was used for more than 5000 samples during clinical pharmacokinetic studies.

Administration, Oral↗
PubMed1983

GLC determination of phendimetrazine in human plasma, serum, or urine.

A sensitive, specific, and quantitative GLC method is described for the determination of phendimetrazine in plasma, serum, or urine. An internal standard was used, which was extracted along with the drug. This mixture then was acetylated to improve the chromatographic separation. A concentration as low as 2 ng/ml of phendimetrazine could be measured from 2 ml of sample using a nitrogen-phosphorous detector. Linearity extended from 2 to 500 ng/ml, and the coefficient of variation was 7%. The method was shown to be applicable to a single-dose bioavailability study.

Biological Availability↗
PubMed1978

Reactions of reduced nicotinamide adenine dinucleotide in acid: studies by reversed-phase high-pressure liquid chromatography.

Reversed-phase high-pressure liquid chromatography was used to isolate acid breakdown products of reduced nicotinamide adenine dinucleotide (NADH) and products produced when NADH breakdown is catalyzed by glyceraldehyde-3-phosphate dehydrogenase (G-3-PD). Chromatographic and UV spectral data on these and related products support a mechanism for NADH acid degradation involving hydroxy addition at the nicotinamide C-6 followed by cyclization of the ring and the adjacent ribose moiety. G-3-PD is shown to catalyze a reaction in which two products are formed which are also intermediates in the acid degradation of NADH (alpha- and beta-6-hydroxynicotinamide products). Formation of the major acid products fits a three-step, first-order mechanism curve, making it possible to calculate the rate constants k2 and k3 as well as the previously determined k1.

Chemical Phenomena↗
PubMed1977

Complementary use of the reversed-phase and anion-exchange modes of high-pressure liquid chromatography for studies of reduced nicotinamide adenine dinucleotide.

The reversed-phase and anion-exchange modes of high-pressure liquid chromatography were used to separate breakdown products and impurities in solutions of the reduced form of nicotinamide adenine dinucleotide (NADH). The two chromatographic modes are compared for studies of NADH. Their use in following the course of acidic breakdown of NADH is described.

Chromatography, High Pressure Liquid↗