Biomedical subjects

K Hettiarachchi

Publications and source records attributed to K Hettiarachchi.

9 recordsLinked to original sources

PubMed2001

Analysis of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane in rat plasma. II. Pharmacokinetic profile in male and female Sprague-Dawley rats evaluated by capillary electrophoresis.

This paper describes a pharmacokinetic study performed in Sprague-Dawley rats after i.v. administration of a single 6-mg/kg dose of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane (Altropane). Plasma samples were collected from the retro-orbital sinus at times up to 3 h after drug administration, extracted by solid-phase extraction, and the drug levels determined by capillary electrophoresis (CE). Pharmacokinetic parameters were determined by a standard noncompartmental model using WinNonlin version 1.5. The maximum plasma concentrations, clearances of the drug, and areas under the curve for male and female rats were 5.74 and 7.26 microg/ml, 135.7 and 98.5 ml/kg x min, and 44.23 and 60.92 microg x min/ml, respectively. The drug was cleared very rapidly from the systemic circulation, with a terminal t(1/2) of 7 to 10 min and a mean residence time of about 11 min for both sexes. The volume of distribution was approximately 1 l/kg. No metabolites were detected when the samples were analyzed individually. However, after samples were pooled and concentrated, traces of two unknown peaks that may represent metabolites were detected in concentrates from the last two timepoints. Part I of this work [J. Chromatogr. A, 895 (2000) 87] describes validation of CE methods for the analysis of aqueous and plasma samples of Altropane, including its solid-phase extraction from rat plasma.

Animals↗

PubMed2001

Characterization and analysis of biphalin: an opioid peptide with a palindromic sequence.

Among the many opioid peptides developed to date as nonaddictive analgesics, biphalin has exhibited extraordinary high potency and many other desirable characteristics. Biphalin is an octapeptide consisting of two monomers of a modified enkephalin, attached via a hydrazine bridge, and with the amino acids assembled in a palindromic sequence. Its structure is (Tyr-D-Ala-Gly-Phe-NH-)-2. However, this unique peptide, like any other synthetic peptide, needs strict quality control because of certain drawbacks associated with peptide synthesis. This paper discusses our approaches to characterizing and analyzing biphalin. Many techniques were used, including elemental analysis, amino acid analysis, amino acid sequence analysis (AASA), mass spectrometry (MS), 1H-NMR, 1H-correlated spectroscopy (COSY)-NMR, high-performance liquid chromatography (HPLC) and capillary electrophoresis (CE). Electrospray ionization (ESI) mass spectrometry, which included both ESI-MS and ESI-MS/MS, was performed to confirm the full sequence because AASA results alone verified only the monomer sequence, and not the full sequence. Although the 1H-NMR results led to a preliminary assignment of many protons, the 1H COSY-NMR results allowed for unequivocal assignment of almost all protons. Peptide purity was determined using two techniques, reversed-phase HPLC and CE. The counter-ion of the peptide, trifluoroacetic acid, was determined by CE, using an indirect detection method developed previously in our laboratory. This paper illustrates successful application of nonconventional techniques to characterize and analyze a structurally modified peptide, biphalin, when standard techniques for peptide analysis are inadequate.

Chromatography, High Pressure Liquid↗

PubMed2000

Analysis of 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nortropane in rat plasma. I. Method development and validation by capillary electrophoresis.

Altropane, 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-(3-iodo-E-allyl)nor tropane, is an imaging agent that was developed recently for early detection of Parkinson's disease. Its promise as a useful radiopharmaceutical for single-photon emission computed tomography or positron emission tomography imaging of the brain has been well demonstrated, and it is currently undergoing clinical trials. This paper presents methods development and validation of capillary electrophoresis (CE) techniques to analyze Altropane in aqueous environments as well as in rat plasma, using an internal standard, nicotinamide. N-Allylaltropane, 2beta-carbomethoxy-3beta-(4-fluorophenyl)-N-allylnortropane, which is a known degradation product of the Altropane precursor (tributyltinaltropane), was used to verify the method's specificity. A solid-phase extraction method for extraction of Altropane from rat plasma is also described. The results presented in this paper demonstrate the applicability of CE methods to study the pharmacokinetic properties of Altropane in animal models. The results of the pharmacokinetic study will be published later, as Part II.

Animals↗

PubMed1998

Capillary electrophoretic determination of acetic acid and trifluoroacetic acid in synthetic peptide samples.

Synthetic peptide samples may contain counter-ions such as acetate or trifluoroacetate as a result of their method of preparation. Furthermore, because acetic acid (HOAc) and trifluoroacetic acid (TFA) are frequently used reagents in peptide synthesis, these acids may be found in synthetic peptide samples as impurities. This paper describes a method validation to determine HOAc and TFA in synthetic peptide samples by capillary electrophoresis (CE) using an internal standard (I.S.) with indirect UV detection. Typical analytical parameters such as precision, linearity, accuracy, specificity, limit of detection and ruggedness were evaluated during the validation. In addition, the contents of HOAc and TFA in two synthetic opioid peptide samples, TIPP[psi] and Orphanin FQ, were determined using the validated method. A unique feature of the method is that it offers determination of both acids in a single assay using a common I.S. The method is very efficient because of relatively short electrophoretic migration times (typically 2 to 8 min) for the acids investigated. This paper also discusses the factors that affect precision in a CE assay.

Acetic Acid↗

PubMed1995

Precision in capillary electrophoresis with respect to quantitative analysis of suramin.

Suramin is an important anti-tumor and anti-viral chemotherapeutic agent. We have previously presented a capillary electrophoresis (CE) method for its quantitative analysis, where its quantitation was linear over three orders of magnitude, with good precision (1.8%) and accuracy. The constantly varying electroosmotic properties of the capillary due to various causes such as analyte adsorption to the inner wall, affect the migration times of analytes during consecutive electrophoresis runs. This results in progressive changes in analyte peak areas, causing less desirable or unacceptable CE assay precision. This paper illustrates a strategy to overcome the problem of assay reproducibility by using an internal standard whose migration time is short and close to that of the analyte so that the relative change of migration time is minimized. Assay precisions as good as 0.3% were observed in these experiments. These results are in agreement with the theoretical basis of experimental capillary electrophoresis.

Antineoplastic Agents↗

PubMed1995

Application of HPLC and CZE to the analysis of polyoxometalates.

Polyoxometalates (POM) are polymers of transition metal oxides. They are widely used as analytical reagents and reaction catalysts. Some have anti-viral properties and are being investigated as anti-HIV agents. Due to solubility and stability limitations, separation methods for POM are rare in the literatures. This paper presents a HPLC and a CZE method for the analysis of sodium tungstate, its equilibrium products and isopolyanions. The methods are simple and sensitive, and can be used to monitor the purity, stability and solution equilibria of POM.

Chromatography, High Pressure Liquid↗

PubMed1991

Capillary electrophoresis analysis of concanavalin A and its succinyl derivative.

A high-performance capillary electrophoresis (CE) system has been developed for concanavalin A (Con A) and its succinyl derivative (SCA). Under the CE system, the tetramer, trimer, dimer, monomer and protein fragments of CA were separated in less than 50 min. SCA was resolved into more than 10 components which were believed to be isomeric succinyl derivatives of Con A. The CE system is a simple and sensitive analytical technique to profile the composition of Con A and SCA preparations. The minimum concentration of Con A in water detectable by the CE system is 1 microgram ml-1.

Concanavalin A↗

PubMedDate not supplied

Quantitative capillary electrophoresis and its application to the polyanionic quinobene.

Factors affecting the accuracy of capillary electrophoresis (CE) assays in general are discussed. Methods to improve the reproducibility and reliability of these assays are suggested. The improvements are demonstrated by developed CE assays for quinobene and suramin. The assays were reproducible (RSD < 2%), accurate (error < 2%), and linear over a concentration range of 1-800 micrograms ml-1 (r2 = 0.999).

Antiviral Agents↗

PubMedDate not supplied

Liquid chromatography and capillary electrophoresis analysis of polyanionic quinobene.

Quinobene is the tetrasodium salt of an organic tetrasulphonic acid. Its unusual solubility characteristics makes the development of LC analysis difficult. However, a specific, precise and accurate LC assay was eventually achieved for quinobene. The assay required gradient elution and was not efficient for quinobene with respect to plate number. As an alternative, a capillary electrophoresis (CE) assay was also developed for quinobene. The CE assay was comparable to the LC assay in precision and accuracy. It was unaffected by the unusual solubility characteristics of quinobene and was more specific, efficient and rugged than the LC assay.

Antiviral Agents↗