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Biomedical subjects

Hideko Kanazawa

Publications and source records attributed to Hideko Kanazawa.

17 recordsLinked to original sources
PubMed2006

A developed determination of midazolam and 1'-hydroxymidazolam in plasma by liquid chromatography-mass spectrometry: application of human pharmacokinetic study for measurement of CYP3A activity.

This paper describes sensitive and reliable determination of midazolam (MDZ) and its major metabolite 1'-hydroxymidazolam (1-OHMDZ) in human plasma by liquid chromatography-mass spectrometry (LC-MS) with a sonic spray ionization (SSI) interface. MDZ, 1-OHMDZ and diazepam as an internal standard were extracted from 1ml of alkalinized plasma using n-hexane-chloroform (70:30, v/v). The extract was injected into an analytical column (YMC-Pak Pro C(18), 50mmx2.0mmi.d.). The mobile phase for separation consisted of 10mM ammonium acetate and methanol (50:50, v/v) and was delivered at a flow-rate of 0.2ml/min. The drift voltage was 100V. The sampling aperture was heated at 120 degrees C and the shield temperature was 260 degrees C. The total time for chromatographic separation was less than 16min. The validated concentration ranges of this method were 0.25-50ng/ml for both MDZ and 1-OHMDZ. Mean recoveries were 93.6% for MDZ and 86.6% for 1-OHMDZ. Intra- and inter-day coefficient variations were less than 6.5 and 5.5% for MDZ, and 6.1 and 5.7% for 1-OHMDZ at 0.3, 4, 20 and 40ng/ml. The limits of quantification were 0.25ng/ml for both MDZ and 1-OHMDZ. This method was sensitive and reliable enough for pharmacokinetic studies on healthy volunteers, and was applied for the measurement of CYP3A activity in humans after an intravenous (1mg) and a single-oral administration (2mg) of subtherapeutic MDZ dose.

Adult↗
PubMed2006

Study of temperature-responsibility on the surfaces of a thermo-responsive polymer modified stationary phase.

We investigated a thermo-sensitive polymer, poly(N-isopropylacrylamide) (PNIPAAm), which is the basis of an HPLC stationary phase. We prepared a PNIPAAm terminally-modified surface. In this study, we investigated the effect of PNIPAAm on the surface of a stationary phase on separation based on changes of the retention time with the temperature step gradient. As the temperature changed the surface property of the stationary phase switched from hydrophilic to hydrophobic. The retention on the polymer-modified stationary phase remarkably changed upon changing the temperature. Using a column packed with PNIPAAm-modified silica, the separation of steroids was carried out by changing the temperature. With increasing temperature, an increased interaction between solutes and PNIPAAm-grafted surfaces of the stationary phases was observed. A temperature-dependent resolution of steroids was achieved using only water as a mobile phase. The PNIPAAm-modified surface of the stationary phase exhibited temperature-controlled hydrophilic-hydrophobic changes. The drastic and reversible surface hydrophilic-hydrophobic property alteration for PNIPAAm terminally-grafted surfaces should be due to rapid changes in the polymer hydration state around the polymer's transition temperature. A solvent gradient elution-like effect could be achieved with a single mobile phase by programmed temperature changes during chromatographic runs. This system should be highly useful to control the function and property of the stationary phase for HPLC only by changing the temperature with an aqueous solvent.

Acrylic Resins↗
PubMed2006

Aqueous chromatography system using pH- and temperature-responsive stationary phase with ion-exchange groups.

We report on the development of a novel analytical HPLC technique of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, ketoprofen and naproxen, with an isocratic aqueous mobile phase. In this study, we designed a new pH- and temperature-responsive copolymer of N-isopropylacrylamide (NIPAAm), butyl methacrylate (BMA) and N,N-dimethylaminopropylacrylamide (DMAPAAm). The copolymer was modified with cross-linked poly(NIPAAm-co-BMA-co-DMAPAAm) (IBD) hydrogel on to aminopropyl silica beads, and the products were evaluated as HPLC packing materials for an ion-exchange- and temperature-responsive chromatography. The property of the surface of the stationary phase was altered from hydrophilic to hydrophobic, and from charged to non-charged by changes in the temperature and pH. In addition, it is possible that ion-exchange groups can appear or be hidden on the polymer chain surface by temperature changes. The interactions of NSAIDs with this stationary phase were controlled by the temperature and the pH with a constant aqueous mobile phase. PH- and temperature-responsive chromatography is expected to be useful for the separation of pharmaceuticals and biomolecules.

Acrylamides↗
PubMed2006

Aqueous chromatography system using temperature-responsive polymer-modified stationary phases.

Extensive research has been carried out on functional polymers which are currently playing important roles in various fields such as medicine and engineering. Such functional polymers which respond to various kinds of stimuli are termed 'intelligent materials'. Poly(N-isopropylacrylamide) (PNIPAAm), a temperature-responsive polymer, was utilized as a chromatography column matrix modifier for a novel chromatographic approach in which only aqueous media are used as a mobile phase. The ability of the developed temperature-responsive chromatography system to separate solutes without using an organic solvent is advantageous from the point of view of maintaining the structure and activity of bioactive compounds. Recently, we designed and synthesized a new pH- and temperature-responsive copolymer as a representative of such environment-responsive polymers and grafted it onto aminopropyl silica beads. The products were evaluated as HPLC packing materials for separation systems based on a new concept, according to which the properties of the stationary phase surface are altered by external stimuli such as pH and temperature. This chromatography system utilizing the PNIPAAm copolymer is very useful for the separation of bioactive substances, such as proteins and peptides, because separation in the aqueous mobile phase is controlled solely by changing the temperature. This analytical system reduces organic waste because no organic solvent is used to separate the solutes and can therefore be classified as environmentally friendly. Future medical and pharmaceutical applications are expected.

Acrylic Resins↗
PubMed2006

Pharmacokinetics of fentanyl after single intravenous injection and constant rate infusion in dogs.

OBJECTIVE: To determine the plasma concentration and define the pharmacokinetic characteristics of fentanyl (10 microg kg(-1)) administered as a single intravenous (IV) injection followed by: (a) no further drug; or (b) a constant rate infusion (CRI) of fentanyl 10 microg kg(-1) hour(-1) lasting 1, 3 or 4 hours in dogs. Animals Fourteen healthy adult beagles (seven males and seven females). EXPERIMENTAL DESIGN: Randomized cross-over design. MATERIALS AND METHODS: Dogs were randomly assigned to four treatment groups. Drugs were administered to each dog in a randomized cross-over design with at least a 14-day washout interval between experiments. All dogs received an IV loading dose of fentanyl (10 microg kg(-1)). One group received no further fentanyl. In others, the loading dose was followed by a CRI of fentanyl (10 microg kg(-1) hour(-1)) for 1, 3 or 4 hours. Blood samples were collected and plasma fentanyl concentrations determined using high-performance liquid chromatography-mass spectrometry. Plasma pharmacokinetic estimates were obtained by plotting plasma concentrations versus time data and by fitting the change in concentration to a pharmacokinetic model, using a purpose-built program written by the Graduate School of Pharmaceutical Sciences (Kyoto University) in Visual Basic (VBA) on Excel (Microsoft Corporation). RESULTS: Plasma fentanyl concentration decreased rapidly after single IV injection: the plasma concentration-time curve best fitted a two-compartment model. Pharmacokinetic variables for IV injection were characterized by a short distribution half-time (t1/2alpha was 4.5 minutes), a relatively long elimination half time (t1/2beta was 45.7 minutes), a large volume of distribution (approximately 5 L kg(-1)) and high total body clearance (77.9 mL minute(-1) kg(-1)). Stable plasma fentanyl levels were obtained in all CRI groups although pharmacokinetic variables were influenced by the duration of administration. CONCLUSIONS AND CLINICAL RELEVANCE: While this study clarified the pharmacokinetic features of rapid IV fentanyl injection and CRI in dogs, the plasma concentration achieving analgesia was not and so further research is needed. Further studies on the effects of other sedatives and/or anaesthetics on fentanyl's disposition are also required as the drug is commonly used with other agents.

Anesthesia, General↗
PubMed2006

Separation of nucleotides with an aqueous mobile phase using pH- and temperature-responsive polymer modified packing materials.

A new method for the qualitative analysis of adenosine nucleotides (AMP, ADP, and ATP) and synthetic oligonucleotides has been proposed, utilizing a pH- and temperature-responsive polymer of N-isopropylacrylamide (NIPAAm), butyl methacrylate (BMA) and N,N-dimethylaminopropylacrylamide (DMAPAAm) as the stationary phase of HPLC. In the chromatographic system using the copolymer with ionizable groups of modified packing materials, we investigated how to separate adenosine nucleotides and oligonucleotides by temperature. The properties of the surface of the copolymer-grafted stationary phase altered from hydrophilic to hydrophobic and from charged to non-charged due to changes in the temperature and in the pH, respectively. In addition, it is possible to exhibit and hide ion-exchange groups on the polymer chain surface by temperature changes. These phenomena result from changes in the charge and hydrophobicity of the pH- and temperature-responsive polymer on the stationary surface with the controlling temperature. A pH- and temperature-responsive chromatography would be greatly useful for biopolymer and nucleotide separation and purification.

Acrylamides↗
PubMed2005

Temperature-responsive stationary phase utilizing a polymer of proline derivative for hydrophobic interaction chromatography using an aqueous mobile phase.

A new method of chromatography is proposed, utilizing a thermo-responsive polymer carrying an amino acid ester residue for the stationary phase of high-performance liquid chromatography (HPLC). We have been investigating the new concept of chromatography, a temperature-responsive chromatography, using temperature-responsive poly(N-isopropylacrylamide) (PNIPAAm)-modified surface for HPLC with a constant aqueous media as the mobile phase. In this study, we designed and synthesized thermo-responsive poly(acryloyl-L-proline methyl ester) and its copolymer with N-isopropylacrylamide (NIPAAm). Homopolymers of acryloyl-L-proline methyl ester and copolymer were prepared by the reaction of radical telomerization. These polymers underwent a reversible phase transition from water-soluble forms into aggregates by changing the temperature, similar to PNIPAAm. The surface properties and functions of stationary phases modified with poly(acryloyl-L-proline methyl ester) were controlled by the external temperature. In the chromatographic system, we separated steroids and amino acids with a variety of hydrophobicities using a sole aqueous mobile phase. In contrast to a PNIPAAm-modified surface, a poly(acryloyl-L-proline methyl ester)-modified surface showed a greater affinity for hydrophobic amino acids.

Chromatography, Liquid↗
PubMed2005

Analysis of herbicides in water using temperature-responsive chromatography and an aqueous mobile phase.

A simple and rapid method has been developed for herbicides in water using temperature-responsive liquid chromatography (LC) and a column packed with poly(N-isopropylacrylamide) (PNIPAAm), a polymer anchored on the stationary-phase surface of modified silica. PNIPAAm reversibly changes its hydrophilic/hydrophobic properties in water in response to temperature. The method was used to determine five sulfonylurea and three urea herbicides. Separation was achieved with a 10 mM ammonium acetate (pH 3.0) isocratic aqueous mobile phase, and by changing the column temperature. The analytes were extracted from water by off-line solid-phase extraction (SPE) with an N-vinyl-pyrrolidone polymer cartridge. The average recoveries of the eight herbicides from spiked pure water, tap water and river water were 70-130% with relative standard deviations (RSDs) of <10%. The limits of quantitation (LOQ) of the eight herbicides were between 1 and 4 microg l(-1).

Acrylic Resins↗
PubMed2005

Electron-transfer mechanism in radical-scavenging reactions by a vitamin E model in a protic medium.

The scavenging reaction of 2,2-diphenyl-1-picrylhydrazyl radical (DPPH.) or galvinoxyl radical (GO.) by a vitamin E model, 2,2,5,7,8-pentamethylchroman-6-ol (1H), was significantly accelerated by the presence of Mg(ClO4)2 in de-aerated methanol (MeOH). Such an acceleration indicates that the radical-scavenging reaction of 1H in MeOH proceeds via an electron transfer from 1H to the radical, followed by a proton transfer, rather than the one-step hydrogen atom transfer which has been observed in acetonitrile (MeCN). A significant negative shift of the one-electron oxidation potential of 1H in MeOH (0.63 V vs. SCE), due to strong solvation as compared to that in MeCN (0.97 V vs. SCE), may result in change of the radical-scavenging mechanisms between protic and aprotic media.

Benzhydryl Compounds↗
PubMed2004

Products of the reaction between alpha- or gamma-tocopherol and nitrogen oxides analyzed by high-performance liquid chromatography with UV-visible and atmospheric pressure chemical ionization mass spectrometric detection.

The reaction products of alpha- or gamma-tocopherol with nitric oxide in the presence of molecular oxygen were isolated and characterized. The consumption of tocopherols and the formation of the major products were monitored by high-performance liquid chromatography (HPLC) by a gradient elution method. The quantitative analysis of these compounds with UV-Vis detectors, however, was interfered by several minor products having similar UV spectra and retention times as those of the major ones. In order to establish a quantitative analytical method for the products, we investigated other detection methods, and found that atmospheric pressure chemical ionization (APCI), LC-MS was a more selective and better analytical method for these compounds.

Atmospheric Pressure↗
PubMed2004

Determination of midazolam and its metabolite as a probe for cytochrome P450 3A4 phenotype by liquid chromatography-mass spectrometry.

This study demonstrated the analysis of midazolam and its metabolites by liquid chromatography-mass spectrometry (LC-MS) with a sonic spray ionization (SSI) interface. The analytical column was a YMC-Pak Pro C18 (50 mm x 2.0 mm i.d.) using 10 mM ammonium acetate (pH 4.8)-methanol (1:1) at a flow rate of 0.2 ml min(-1). The drift voltage was 100 V. The sampling aperture was heated at 110 degrees C and the shield temperature was 230 degrees C. The lower limits for the detection of midazolam and 1'-hydroxymidazolam were 26.3 and 112.76 pg injected, respectively. The calibration curves for midazolam and 1'-hydroxymidazolam were linear in the range of 0.1-5 microg ml(-1). Within-day relative standard deviations was less than 7%. The method was applied to the determination of midazolam in monkey plasma, and the analysis of midazolam and its metabolites in an in vitro study with recombinant cytochrome P450 (CYP) 3A4. This method is sufficiently sensitive and useful to elucidate the kinetics of midazolam metabolite formation. We also investigated the effect of propofol on the metabolism of midazolam using recombinant CYP3A4. Propofol competitively inhibited the metabolism of midazolam to 1'-hydroxymidazolam by CYP3A4.

Animals↗
PubMed2004

Temperature- and pH-responsive aminopropyl-silica ion-exchange columns grafted with copolymers of N-isopropylacrylamide.

We have designed copolymers of N-isopropylacrylamide, environmentally-responsive polymers, which respond to temperature and other external stimuli. In this study, we designed and synthesized copolymers that introduced ion-exchange groups. These copolymers responded to the temperature and the pH, and the copolymer-grafted aminopropyl silica beads were used as HPLC packing materials. This stationary phase altered the properties from hydrophilic to hydrophobic and from charge to non-charge by temperature and pH changes. We studied the separations of organic acids and phenylthiohydantoin-amino acids using environmentally-responsive chromatography, and confirmed the effects of the ion-exchange groups. The elution behaviors of these samples were controlled by the temperature changes without organic solvents in the mobile phase. It was confirmed that the interactions between the solute and stationary phase could be freely controlled by the temperature and the pH. Environmentally-responsive chromatography is expected to be applicable to the separation of pharmaceuticals and biomolecules, such as peptides, proteins and nucleic acids.

Acrylamides↗
PubMed2003

Stereospecific analysis of omeprazole in human plasma as a probe for CYP2C19 phenotype.

Omeprazole is a class referred to as proton pump inhibitor; it acts to regulate acid production in the stomach and is used to treat various acid-related gastrointestinal disorders. In the liver, it is metabolized to varying degrees by several cytochrome P-450 (CYP) isoenzymes which are further categorized into subfamilies of related polymorphic gene products. The metabolism of omeprazole is to a large extent dependent on CYP3A4 and CYP2C19. Omeprazole is metabolized to two major metabolites, 5-hydroxyomeprazole (CYP2C19) and omeprazole sulfone (CYP3A4). Minor mutations in CYP2C19 affect its activity in the liver and, in turn, the metabolic and pharmacokinetic profiles of omeprazole. The frequency of CYP2C19 poor metabolizers in population of Asian descent has been reported to range from 10 to 20%. Accordingly, results from population studies indicate that omeprazole can be used as a probe drug for phenotyping CYP2C19. The optical isomers of omeprazole show a clear difference in their metabolism by human liver microsomes. This study demonstrates the stereospecific analysis of omeprazole in human plasma as a probe drug of CYP2C19 phenotyping. The chiral separation of omeprazole was achieved on a chiral column with circular dichroism (CD) detection and LC/MS. A good resolution of enantiomers was obtained. The column used for chiral separation was CHIRALPAK AD-RH column (4.6 x 150 mm) using phosphate buffer and (or ammonium acetate) acetonitrile as an eluent. After a single oral dose of omeprazole (20 mg), the plasma concentrations of the separate enantiomers of omeprazole were determined for 3.5 h after drug intake. The present study is useful because of the part polymorphism plays in the therapeutic effectiveness of proton pump inhibitors during the treatment of acid-related diseases.

Aryl Hydrocarbon Hydroxylases↗
PubMed2002

Determination of omeprazole and its metabolites in human plasma by liquid chromatography-mass spectrometry.

Omeprazole is a benzimidazole compound that acts as a proton-pump inhibitor. Because the metabolism of omeprazole is mainly catalyzed by cytochrome P-450 (CYP) 3A4 and CYP2C19. the genetic polymorphism of CYP2C19 could be of clinical concern in the treatment of acid-related diseases with omeprazole. Therefore, a reliable method for omeprazole phenotyping is desirable in clinical situations. This study has demonstrated the determination of omeprazole and its metabolites in human plasma by liquid chromatography-three-dimensional quadrupole mass spectrometry with a sonic spray ionization interface. The analytical column was YMC-Pack Pro C18(50x2.0 mm I.D.) using acetonitrile-50 mM ammonium acetate (pH 7.25) (1:4) at a flow-rate of 0.2 ml/min. The drift voltage was 30 V. The sampling aperture was heated at 110 degrees C and Shield temperature was 230 degrees C. In the mass spectrum, the molecular ions of omeprazole, hydroxyomeprazole and omeprazole sulfone were clearly observed as base peaks. This method is sufficiently sensitive and accurate for pharmacokinetic studies of omeprazol.

Anti-Ulcer Agents↗
PubMed2002

Stereospecific analysis of loxoprofen in plasma by chiral column liquid chromatography with a circular dichroism-based detector.

The chiral separation of loxoprofen was achieved on a chiral column with UV and circular dichroism (CD) detection. The good resolution of four loxoprofen stereoisomers was obtained. The column used for the chiral separation was Chiralcel OJ column (250 x 4.6 mm) using hexane-2-propanol-trifluoroacetic acid (95:5:0.1), as an eluent. The flow-rate was 1.0 ml/min and the detection was at 225 nm. In addition, CD and UV spectra were obtained by stopped flow scanning. The method allows the determination of the stereoisomers of loxoprofen in human plasma after the administration of therapeutic dose of the racemic drug, thus HPLC with CD detector is useful for the stereospecific determination of loxoprofen products in biological samples.

Anti-Inflammatory Agents, Non-Steroidal↗
PubMed2002

Temperature-responsive chromatography using poly(N-isopropylacrylamide) hydrogel-modified silica.

Poly(N-isopropylacrylamide) (PNIPAAm) has the sharpest phase transition of the class of thermo-sensitive N-alkyl acrylamide polymers. We developed a new method of HPLC using packing materials modified with cross-linked poly(N-isopropylacrylamide) (PNIPAAm) hydrogel. A temperature-responsive surface was prepared by polymerization of NIPAAm in the presence of a cross-linker on the silica support. The surface properties and functions of the stationary phases change in response to the external temperature. Therefore it easily changes the interaction of a solute with the surface with a constant aqueous mobile phase. A temperature-responsive elution behavior was observed on the separation of steroids and PTH-amino acids. The method is expected to be applicable to separation in the pharmaceutical and biomedical fields.

Acrylamides↗