Search PubMed⌕ Search

Biomedical subjects

L A Sternson

Publications and source records attributed to L A Sternson.

At least 37 records · Page 2Linked to original sources
PubMed1983

Analysis of riboxamide in plasma by high-performance liquid chromatography using automated column switching.

A sensitive and highly specific assay for riboxamide (TCAR) in human and canine plasma is described. The specificity of the procedure is derived from the method of sample preparation and a high-performance liquid chromatographic separation which utilizes the different selectivities of two columns. Partial separation of TCAR from plasma is achieved on a solvent-generated anion exchanger with silica gel as the solid support. The separation is completed by switching the eluent fraction containing TCAR from the first column to a second solvent-generated anion exchanger which has ODS-silica as its support. The relationship between the amount of drug injected and its peak height was linear over wide ranges of concentrations (0-10 micrograms/ml) and injection volumes (20-200 microliter). The limit of detection for TCAR in plasma was 40 ng/ml which can be detected by injecting 200 microliter of processed plasma. The recoveries from plasma were 100.2 +/- 0.9% and 101.3 +/- 2.3% when spiked at the 10 and 1 microgram/ml levels, respectively. The applicability of the method to pharmacokinetic studies was demonstrated by following the plasma levels of TCAR after intravenous administration in the dog.

Animals↗
PubMed1983

Evaluation of reductive amperometric detection in the liquid chromatographic determination of antineoplastic platinum complexes.

The usefulness of reductive electrochemical detection at mercury drop electrodes has been determined for platinum complexes separated by solvent-generated anion-exchange high-performance liquid chromatography. Both current-sampled dropping mercury and hanging mercury drop electrodes (DME and HMDE) provide significant advantages over UV absorbance and off-line non-flame atomic absorption detection. The effects of chromatographic and polarographic parameters on analytical system performance have been investigated. By raising the detector cell temperature, the detector response to cis-dichlorodiammineplatinum(II) (DDP) can be shifted anodically to 0.0 V vs. Ag/AgCl, thereby increasing detector selectivity for this compound. The noise-limited minimum detectable quantities of DDP with DME and HMDE are 1.8 ng and 70 pg injected, respectively. DDP can be determined in untreated urine at levels below 100 ng/ml.

Chromatography, High Pressure Liquid↗
PubMed1983

Monitoring the reactions of cisplatin with nucleotides and methionine by reversed-phase high-performance liquid chromatography using cationic and anionic pairing ions.

Methodology, based on reversed-phase high-performance liquid chromatography, is described for monitoring the reactions of cisplatin with DNA, nucleotides, and methionine. Cisplatin was determined in DNA ultrafiltrates on solvent-generated anion exchangers which were prepared by coating the surface of a reversed-phase column with hexadecyltrimethylammonium bromide. These systems were also applicable to studies on the reactions of cisplatin with nucleotides. The retention of the nucleotides studied (5'-AMP, 5'-GMP, 5'-CMP, and 5'-TMP) was described by means of an ion-exchange model and was manipulated by controlling the phosphate concentration in the mobile phase and its pH. The results indicate that cisplatin interacts predominantly with adenosine and guanosine groups on the DNA molecule and that binding is limited by the rate of conversion to an aquated intermediate. Whereas reversed-phase HPLC systems employing cationic pairing ions were applicable to the analysis of mixtures containing cisplatin and anionic solutes, systems employing alkyl sulfonates were required to monitor the reaction of cisplatin with methionine which produces cationic products. Retention, in this latter system, was optimized by the addition of acetonitrile to the mobile phase and by controlling the concentration and chain length of alkylsulfonate in the mobile phase. Although an octadecylsilylsilica, reversed-phase column was preferred for the analytical separation of the methionine-platinum complexes, a polystyrene-divinylbenzene colume was preferred for preparative work.

Anions↗
PubMed1983

High-performance liquid chromatography of cisplatin.

The retention behavior of cisplatin on a variety of stationary phases has been investigated using aqueous mobile phases modified by the addition of various electrolytes and methanol. Cisplatin is poorly retained on reverse-phase or silica columns but satisfactorily retained on chemically bonded or solvent-generated anion exchangers. The retention of the neutral complex on positively charged stationary phases is explained in terms of ion-dipole interactions and rationalized by the application of solvophobic theory. The use of solvent-generated anion exchangers for the analysis of cisplatin offers significant advantages over the chemically bonded system in terms of peak shape, column efficiency, and stability. By the use of column switching and off-line atomic absorption, solvent-generated anion exchange high-performance liquid chromatography (HPLC) is applicable to the determination of cisplatin in urine.

Chromatography, High Pressure Liquid↗
PubMed1983

Factors affecting the stability of fluorescent isoindoles derived from reaction of o-phthalaldehyde and hydroxyalkylthiols with primary amines.

The stability of a series of fluorescent isoindole derivatives formed in situ under analytical conditions following the reaction of o-phthalaldehyde (OPA) and 2-mercaptoethanol (2-ME) with a series of primary amines are reported. Increasing the bulk and degree of substitution at C-10 of the resulting isoindole resulted in substantial increases in product stability. The effects of excess OPA and 2-ME on isoindole stability were examined and OPA was observed to catalyze isoindole degradation while 2-ME had no effect. Previously proposed degradation mechanisms were reexamined in light of the present data and an alternate degradation pathway is proposed. 3-Mercapto-1-propanol (3-MP) was found to be a superior thiol for use in the fluorogenic OPA reaction. The OPA/3-MP reagent combination was utilized to derive several amino acids and offered detection limits (S/N = 2) of less than 200 fmol.

Aldehydes↗
PubMed1983

Cation exchange contribution to the retention of specific quaternary ammonium compounds in reversed-phase high-performance liquid chromatography.

The influence of electrolytes on the retention of organic cationic solutes in reversed-phase high-performance liquid chromatography (RP-HPLC) has been investigated. The effects of the nature and concentration of electrolytes and mobile phase pH on the retention of two model quaternary ammonium compounds were studied on mu-Bondapak C18 stationary phase with aqueous methanolic eluents. The nature and concentration of inorganic cations added to the mobile phase modified the retention of the solutes. The counter anion of the added electrolyte did not perceptibly influence solute retention at constant mobile phase pH, although it did significantly influence solute retention when the electrolytes were added to unbuffered mobile phases. The retention data are consistent with the inclusion of an ion exchange contribution to the retention of cationic solutes in the systems investigated.

Journal Article↗
PubMed1983

Factors affecting the retention of quaternary ammonium ions in reversed-phase high-performance liquid chromatography.

The influence of solute structure (charge and hydrophobic substitution), organic modifier (type and concentration) and ion-pairing agent on the retention of nine quaternary- and bis-quaternary ammonium ions has been investigated in reversed-phase HPLC on ODS-silica. A functional group approach was taken to elucidate the influences of substitution on the charged nitrogen and the addition of a second positive charge to the solute molecule. These and other factors contributing to solute retention are discussed within the context of solvophobic theory. Hydrophobic effects and the solvation of the charged centre are shown to be the major factors contributing to retention in non-ion pair eluents. In addition, various electrostatic interactions in the mobile and stationary phases may contribute to solute retention in eluents containing an ion-pairing agent. It was found that ternary eluents containing hexane sulphonic acid and two organic modifiers offer certain selectivity advantages when compared with binary eluents.

Journal Article↗
PubMed1983

Some strategies for improving specificity and sensitivity in the analysis of anti-cancer drugs.

Some approaches are discussed for introducing specificity and sensitivity into analytical methods for anti-tumour agents which include a liquid chromatographic step. Various modes of HPLC have been exploited to monitor these drugs specifically and at therapeutically low levels. The use of column switching technology and chemical derivatization techniques to enhance both specificity and sensitivity are discussed. Multiple columns (linked through switching valves) containing packings exhibiting different affinities for the analytes cisplatin and riboxamide provide (a) a high degree of selectivity with convenient analysis times, (b) the opportunity for preconcentration of analytes, (c) improved longevity of analytical columns, (d) a solution to the 'general elution problem', and (e) allow direct application of biological fluid to the HPLC system. The use of chemical derivatization techniques (pre- and post-column) to achieve improved sensitivity and altered chromatographic and chemical properties of these and other anti-tumour agents (galactitol, tamoxifen, emetine) is also described. The high chemical reactivity of many anti-tumour agents often requires their rapid derivatization after a biological sample is drawn to prevent chemical degradation in the sample vial. The use of chemical and photochemical derivatization techniques combined with spectrophotometric, fluorometric and voltammetric detectors illustrates the power and utility of derivatization technology in trace drug analysis.

Journal Article↗
PubMed1983

Trace analysis for cis-platinum anti-cancer drugs via LCEC.

Liquid chromatography-electrochemical detection (LCEC) methods and instrumentation have been successfully applied for the trace determination of at least three separate platinum (Pt) anti-cancer (neoplastic) agents. All of these compounds have proven clinically effective in the treatment of human neoplasms. The three Pt derivatives studied were: cis-dichloro diammine platinum (cis-Pt); cis-diammine-1, 1-cyclobutane dicarboxylate platinum (CBDCA); and cis-dichloro-trans-dihydroxy diisopropylamine platinum (CHIP). The parent compound, cis-Pt (CDDP), can be determined via both oxidative and reductive LCEC, with differences in the minimum limits of detection. Calibration plots and minimum detection limits have been determined for all three derivatives. Both CBDCA and CHIP can be determined via direct LCEC, but the minimum detection limits for CBDCA are not practical for stability or clinical studies. A new method of derivatization for CBDCA and related Pt compounds has been developed, wherein this can be quantitatively converted to cis-Pt, and the final derivative is then determined as for the parent cis-Pt. CDDP can be determined via reductive LCEC at the 100-ppb level in plasma. The final methods of LCEC analysis have now been applied to a variety of stability studies with all three Pt drugs, in water, plasma, and saline infusion solutions. It is suggested that these LCEC methods are directly applicable and amenable to "real world" clinical settings and cancer-patient samples.

Chromatography, Liquid↗
PubMed1983

Tumor concentration of platinum in patients with head and neck cancer.

Simultaneous concentrations of total plasma platinum, filterable platinum, intact cisplatin, and total tumor platinum were measured for 24 hours after an intravenous bolus of cisplatin in five patients. Tumor concentrations of drug were greater than could be explained on the basis of circulating plasma platinum at the time of biopsy. Intratumor platinum concentrations derived from this study provide guidance for selection of the appropriate drug concentrations for in vitro chemosensitivity testing of head and neck cancer in humans.

Animals↗
PubMed1982

The effect of amine structure on complexation with lasalocid in model membrane systems. II. Ionophore selectivity for amines in lipid bilayers and at oil/water interfaces.

The ionophore antibiotic X-537A (lasalocid) transports biogenic amines across biological and artificial membranes. The major portion of amine flux (greater than 99%) occurs as a 1:1 neutral complex. The rank order of ionophore selectivity was determined for lipid bilayer membrane transport of amines based on a comparison of permeability coefficients: p-tyramine approximately beta-phenylethylamine approximately amphetamine greater than methamphetamine greater than dopamine greater than phenylephrine approximately metanephrine greater than norepinephrine greater than epinephrine. This rank order is in agreement with results obtained from partitioning measurements which were carried out in parallel to the bilayer membrane experiments. A correlation between amine structure and binding characteristics has been developed.

Amines↗
PubMed1982

High-performance liquid chromatography of platinum complexes on solvent generated anion exchangers. III. Application to the analysis of cisplatin in urine using automated column switching.

Platinum complexes are retained on solvent generated anion exchangers, prepared by coating reversed-phase (C-18) supports with a monolayer of hexadecyltrimethylammonium bromide. The retention mechanism is described in terms of ion--dipole interactions in the stationary phase, reinforced by a hydrophobic effect. The high degree of ligand selectivity exhibited by these systems arises from the use of purely aqueous mobile phases which maximize the differences in solute dipole and hydrophobic surface area. By using stationary phases of different surface characteristics and the application of automated column switching, the technique is applicable to the clinical analysis of cisplatin in urine. After chromatography, the purified cisplatin fractions area determined by atomic absorption spectrophotometry. The recovery of cisplatin from urine is 101.1% with a relative standard deviation of 3.6% and the limit of detection is 2 micrograms/ml.

Automation↗
PubMed1982

The effect of amine structure on complexation with lasalocid in model membrane systems. I. Identification of charged complexes in lipid bilayer membranes.

The electrical properties of X-537A (lasalocid) doped lipid bilayer membranes were studied in the presence of a series of nine biogenic amines which contain beta-phenylethylamine as the basic structural unit. The ionophore antibiotic was found to form charged complexes within the membrane during the transport of some of the amines. The dependence of membrane conductance on the concentration of ionophore and amine was studied. The amines are divided into three classes according to the nature of the complexes formed: (1) charged complex involving two ionophores (phenylephrine, metanephrine, and amphetamine); (2) charged complex containing three ionophores (dopamine, norepinephrine and epinephrine); and (3) no charged species formed (p- and m-tyramine and beta-phenylethylamine).

Biogenic Amines↗
PubMed1981

Clinical analysis for the anti-neoplastic agent 1,4-dihydroxy-5,8-bis((2-[(2-hydroxyethyl)amino]ethyl)-amino)9,10-anthracenedio ne dihydrochloride (NSC 301739) in plasma. Application of temperature control to provide selectivity in paired-ion high-performance liquid chromatography.

An analytical method is described which permits monitoring of plasma level of the anti-tumor agent 1,4-dihydroxy-5,8-bis((2-[(2-hydroxyethyl)amino]ethyl)amino)9,10-antracenedione dihydrochloride (DHAD) following its intravenous administration to cancer patients. The drug cannot be efficiently extracted from plasma into water-immiscible solvents, but is effectively separated from the biological matrix by retention on hydrophobic XAD-2 beads packed in a disposable glass cartridge. DHAD is subsequently selectively eluted from this column and then analyzed by reversed-phase partition chromatography with spectrophotometric detection of the analyte. Resolution of overlapping bands during high-performance liquid chromatographic separation was achieved by systematic optimization of mobile phase, ion-pairing agent and temperature. A possible explanation for the observed selectively provided by temperature adjustment is offered. Plasma levels in the range of 75--3000 ng of DHAD per ml (7.5--300 ng applied to the column) can be analyzed with a precision of less than +/- 10%. Total recovery of drug from plasma is ca. 95%.

Anthracenes↗
PubMed1981

Clinical kinetics on intact cisplatin and some related species.

Plasma concentrations of cisplatin, total platinum, and total filterable platinum were monitored in 24 patients after either 50 or 100 mg/m2 of cisplatin by rapid intravenous injection. Half the patients at each dose were pretreated with mannitol. Total platinum levels declined in a triphasic fashion with a terminal half-life (t1/2)greater than or equal to 24 hr. Both total filterable platinum and cisplatin levels declined in a monophasic manner and exhibited t1/2 of 0.3 to 0.5 hr. The ratio of cisplatin to total filterable platinum in plasma remained constant (0.6 to 0.8) over the time period (2 hr) during which they could be detected, while the ratio of the plasma levels of cisplatin to total platinum decreased continuously from approximately 0.5 at 5 min to approximately 0.10 at 2 hr. Larger doses of cisplatin resulted in higher plasma levels of all three species monitored, and although the increases appeared somewhat less than proportional to dose, terminal plasma slopes were not dose dependent. Neither mannitol nor dose had an effect on the various species ratios, nor did mannitol appear to affect either plasma levels or terminal plasma decline.

Cisplatin↗