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Biomedical subjects

C M Riley

Publications and source records attributed to C M Riley.

At least 73 records · Page 4Linked to original sources
PubMed1987

The stability of carboplatin in ambulatory continuous infusion regimes.

Several anti-cancer agents are administered by continuous infusion in an attempt to improve the therapeutic index obtained with solid tumours. In Exeter this approach, combined with the use of ambulatory infusion pumps, forms the basis of a home oncology programme in which a complete course of medication in pre-filled syringes is supplied on an out-patient basis. It is essential to ensure that the drug remains stable during storage prior to use and also during infusion where the temperature of the drug solution in a holster-worn ambulatory pump can reach 37 degrees C. In this study the stability of a carboplatin infusion (20 mg in 2 ml) in pre-filled syringes under storage and in-use conditions was determined using a stability-indicating HPLC assay. There was no loss of carboplatin from pre-filled syringes stored at 4 degrees C for 5 days. At 37 degrees C, the loss of carboplatin was 3.1% over 24 h.

Antineoplastic Agents↗
PubMed1987

Selected aspects of the development of methods for the analysis of drugs by high performance liquid chromatography.

The successful analysis of drugs in biological fluids and other matrices by reversed phase high performance liquid chromatography (h.p.l.c.) relies upon the optimization of the chromatographic separation, the sample preparation and the post-column detection. Recent advances in the detection and derivatisation of exogenous substances are described elsewhere in this volume (Sternson 1986). This paper deals with selected aspects of the optimization of the chromatographic separation, concentrating on the theoretical basis and practical application of mobile phase selectivity in reversed phase ion-pair systems. In addition, recent advances in sample preparation techniques which permit the direct injection of biological fluids are discussed.

Amines↗
PubMed1986

In vitro studies with melphalan and pediatric neoplastic and normal bone marrow cells.

Chemotherapeutic agents are used in increasingly high dosages to treat patients with refractory cancers. An in vitro clonogenic assay was used to investigate the effects of melphalan on cultures of human neuroblastoma, Ewing's sarcoma, and osteosarcoma cells, as well as on normal bone marrow cells. A 1-hr incubation with 10(-5) M melphalan significantly inhibited tumor colony growth of both fresh neuroblastoma and osteosarcoma cells (p less than 0.01) while Ewing's sarcoma cells and normal bone marrow appeared resistant to melphalan even at a 100-fold higher concentration. Incubation with melphalan for 8 hr did not significantly increase the sensitivity of neuroblastoma and osteosarcoma or the relative resistance of Ewing's sarcoma cells; however, normal bone marrow which had remained resistant to melphalan after 1 hr of incubation, showed significant inhibition of colony growth after an 8-hr incubation with the agent. Repeated exposure to melphalan increased the degree of inhibition of both tumor and normal marrow colonies. Fresh neuroblastoma cells were significantly more sensitive than long-term cultured neuroblastoma cells at all drug doses tested. HPLC studies demonstrated that the loss of melphalan followed first-order kinetics with a half-life of 69 min, and that in addition to the 2 known breakdown products, mono- and dihydroxy-melphalan, several other peaks were present which were not attributable to the tissue culture medium or the buffer solutions.

Bone Marrow↗
PubMed1986

Determination of ketoconazole in the plasma, liver, lung and adrenal of the rat by high-performance liquid chromatography.

An accurate and precise procedure for the rapid analysis of ketoconazole in the lung, liver, plasma and adrenal gland of the rat has been developed. Separation of the drug from endogenous substances was achieved by solid-phase extraction followed by reversed-phase chromatography on a Novapak C18 column using a mobile phase of methanol--acetonitrile--0.02 M phosphate buffer (pH 6.8) (35:30:35). Depending on the tissue, the recoveries of ketoconazole and clotrimazole, which was used as an internal standard, ranged between 85.0 to 93.6% and 79.3 to 84.1%, respectively. The reproducibility of the assay was between 3 and 4%, depending on the tissue involved. The sensitivity of the procedure permitted the monitoring of ketoconazole levels for up to 24 h in the adrenal and up to 48 h for plasma, lung and liver, following oral administration of 150 mg/kg of the drug to male rats.

Adrenal Glands↗
PubMed1986

Stability of intravenous admixtures containing aztreonam and cefazolin.

The stability of aztreonam and cefazolin in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection in polyvinyl chloride containers: aztreonam 20 mg/mL and cefazolin 20 mg/mL (as the sodium salt); aztreonam 10 mg/mL and cefazolin 5 mg/mL; aztreonam 20 mg/mL and cefazolin 5 mg/mL; and aztreonam 10 mg/mL and cefazolin 20 mg/mL. One of each of these admixtures was stored at 23-25 degrees C for 48 hours and at 4-5 degrees C for seven days. At various storage times the admixtures were inspected for visual changes, and 1-mL samples were tested for pH and assayed using a stability-indicating high-performance liquid chromatographic assay. No visual changes were observed, and changes in pH were negligible. Concentrations of aztreonam and cefazolin under both storage conditions decreased by less than 3%. Intravenous admixtures of aztreonam and cefazolin at the concentrations studied are stable for at least 48 hours at 23-25 degrees C and for seven days at 4-5 degrees C.

Aztreonam↗
PubMed1986

Stability of intravenous admixtures of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin.

The stability of aztreonam and cefoxitin, gentamicin, metronidazole, or tobramycin in intravenous admixtures containing aztreonam and one of the other drugs was studied. Admixtures of aztreonam and gentamicin, aztreonam and tobramycin, and aztreonam and cefoxitin were each prepared in four different concentrations in both 0.9% sodium chloride injection and 5% dextrose injection. Admixtures of aztreonam and metronidazole were prepared in two different concentrations using a commercially available solution of metronidazole 5 mg/mL in a phosphate-citrate buffer. One of each of these admixtures was stored at 25 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times, 1-mL samples of the admixtures were tested for pH and assayed using high-performance liquid chromatography or fluorescence polarization immunoassay. The pH of all admixtures except admixtures of aztreonam and cefoxitin decreased only slightly during storage. Concentrations of aztreonam and tobramycin under both storage conditions decreased by less than 10%. Concentrations of cefoxitin and aztreonam decreased by more than 10% at 25 degrees C, and concentrations of gentamicin decreased by more than 10% under both storage conditions. Visual inspection of admixtures of aztreonam and metronidazole revealed an incompatibility between the two drugs, as evidenced by the appearance of a cherry-red color. Admixtures of aztreonam 10 and 20 mg/mL and tobramycin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 48 hours at 25 degrees C or seven days at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and gentamicin 0.2 and 0.8 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for eight hours at 25 degrees C and 24 hours at 4 degrees C. Admixtures of aztreonam 10 and 20 mg/mL and cefoxitin 10 and 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection are stable for 12 hours at 25 degrees C and seven days at 4 degrees C. Aztreonam and metronidazole should be administered separately.

Aztreonam↗
PubMed1986

Interaction of aztreonam with nafcillin in intravenous admixtures.

An interaction between aztreonam and nafcillin sodium in 0.9% sodium chloride injection or 5% dextrose injection stored in glass or plastic containers is reported. During preliminary experiments, admixtures of aztreonam 10 or 20 mg/mL and nafcillin sodium 10 or 20 mg/mL in 0.9% sodium chloride injection or 5% dextrose injection prepared in glass flasks became cloudy and showed evidence of a fine precipitate. Drug concentrations were measured with a stability-indicating high-performance liquid chromatographic (HPLC) assay. Admixtures of aztreonam 20 mg/mL and nafcillin sodium 20 mg/mL in 5% dextrose injection or 0.9% sodium chloride injection were prepared in polyvinyl chloride bags and stored at room temperature (23-25 degrees C) for 48 hours. The admixtures were assayed at 0, 24, and 48 hours with the same HPLC procedure used during the pretesting experiments. The precipitates were isolated, washed, and centrifuged; the supernatant was analyzed by HPLC assay, and the final residue was analyzed by nuclear magnetic resonance (NMR) spectroscopy. The initial recoveries of drug from the pretesting experiments ranged from 99.2 to 102.4%. Analysis of the precipitates indicated that the precipitate was neither a salt nor a complex formed by the physical interaction of aztreonam and nafcillin sodium, but probably a high-molecular-weight polymer formed by the covalent bonding of subunits of the formulation components. Substantial losses of both drugs from the admixtures were evident after 48 hours of storage. The precipitate was observed sooner in the admixtures containing 0.9% sodium chloride injection than in the admixtures prepared in 5% dextrose injection.(ABSTRACT TRUNCATED AT 250 WORDS)

Aztreonam↗
PubMed1985

Analysis of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (bentiromide) metabolites in urine by ion-pair high-performance liquid chromatography.

A high-performance liquid chromatographic method is described for the analysis of bentiromide metabolites in urine. The procedure involves no more than direct injection of the diluted urine sample, obviating the need for an extraction step or an internal standard. A mu Bondapak C18 column is used with a mobile phase of 0.01 M tetrabutylammonium chloride (pH 7.4)--methanol (9:1). A flow-rate of 1.4 ml/min, detection at 254 nm and column temperature of 40 degrees C are employed. These conditions were achieved by investigating the effects of mobile phase pH, and concentrations and types of organic modifiers, buffers and ion-pairing agents on the resolution of the metabolites. The analysis time is 18 min per sample and the coefficient of variation on replicate assays is less than 10% for most concentrations studied. Analytical recoveries were between 95 and 100% throughout the appropriate concentration ranges and no interferences were obtained with the exception of p-acetamidobenzoyl glucuronide which could be eliminated by treatment of the samples with beta-glucuronidase. Concentration profiles of the metabolites were studied in normal subjects, and the method was found to be potentially useful for clinical situations in which the existing bentiromide test leads to ambiguous results because of small bowel and hepatic dysfunctions.

4-Aminobenzoic Acid↗
PubMed1985

Stability of intravenous admixtures of aztreonam and ampicillin.

The stability of aztreonam and ampicillin in intravenous admixtures containing both drugs was studied. Each of the following drugs and combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 10 and 20 mg/mL, ampicillin sodium 5 and 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 20 mg/mL, aztreonam 20 mg/mL and ampicillin sodium 5 mg/mL, aztreonam 10 mg/mL and ampicillin sodium 20 mg/mL, and aztreonam 10 mg/mL and ampicillin sodium 5 mg/mL. One of each of these admixtures was stored at 25 degrees C for 48 hours and 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 2-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed by high-performance liquid chromatography. No visual changes were observed. In the two-drug solutions, pH was influenced by concentrations of the two drugs and stability of the drugs was influenced by the solution pH. The pH of single-drug aztreonam admixtures did not change during storage, but the pH of single-drug and two-drug admixtures containing ampicillin decreased. In single-drug admixtures, aztreonam loss under both storage conditions was less than 10% but ampicillin loss was more than 10% in 0.9% sodium chloride injection and more than 50% in 5% dextrose injection. The stability of ampicillin was increased in the presence of aztreonam, and the stability of aztreonam was decreased in the presence of ampicillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Ampicillin↗
PubMed1985

Stability of intravenous admixtures of aztreonam and clindamycin phosphate.

The stability of aztreonam and clindamycin phosphate in intravenous admixtures was studied. Each of the following combinations of drugs was added to both 5% dextrose injection and 0.9% sodium chloride injection: aztreonam 20 mg/mL and clindamycin phosphate 6 mg/mL; aztreonam 20 mg/mL and clindamycin phosphate 3 mg/mL; aztreonam 10 mg/mL and clindamycin phosphate 6 mg/mL; and aztreonam 10 mg/mL and clindamycin phosphate 3 mg/mL. One of each of these admixtures was stored at 22-23 degrees C for 48 hours and at 4 degrees C for seven days. At various storage times the admixtures were inspected for visual changes and 1-mL samples were examined microscopically for crystalline and particulate matter, tested for pH, and assayed using high-performance liquid chromatography. No visual changes were observed. The pH of admixtures decreased only slightly during storage. Concentrations of aztreonam and clindamycin phosphate under both storage conditions decreased by less than 10%. Intravenous admixtures of aztreonam and clindamycin phosphate at the concentrations studied are stable for at least 48 hours at 22-23 degrees C and at least seven days at 4 degrees C.

Ampicillin↗
PubMed1984

The determination of metoclopramide in plasma by reversed-phase ion-pair high-performance liquid chromatography.

Methodology based on reversed-phase ion-pair high-performance liquid chromatography is described for the determination of metoclopramide in plasma. The chromatography was optimized in terms of the peak shape for the drug and its resolution from endogenous plasma components by investigating the effects of quaternary ammonium (competing) ions and alkylsulphate (pairing) ions in an acidic mobile phase containing acetonitrile (20%) and 20 mM acetic acid. Optimum chromatographic conditions were obtained with an ODS-Hypersil column and a mobile phase containing 20% acetonitrile, 20 mM acetic acid, 0.6 mM sodium octylsulphate and 0.5 mM tetrabutylammonium chloride. A simplified method of sample preparation is described in which only 1 ml of plasma is required. The limit of detection (at 310 nm) was 7 ng/ml and no interference from endogenous plasma components or from any drugs commonly used in the treatment of cancer was observed. Consequently the methodology should be applicable to pharmacokinetic studies on metoclopramide, when used clinically to control the gastro-intestinal side-effects of chemotherapy.

Journal Article↗
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

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 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↗