Biomedical subjects

Mihoko N Nakashima

Publications and source records attributed to Mihoko N Nakashima.

17 recordsLinked to original sources

PubMed2007

Determination of paclitaxel in human and rat blood samples after administration of low dose paclitaxel by HPLC-UV detection.

A simple and sensitive HPLC-UV method was developed for the determination of paclitaxel (TXL) in human and rat blood samples. 4-Hydroxybenzoic acid n-hexyl ester was used as an internal standard. TXL was extracted by a liquid-liquid extraction with tert-butylmethyl ether. The disturbing peaks in the case of serum sample were removed by pre-extraction with hexane. The separation of TXL was achieved within 25 min using an ODS column with 50% acetonitrile aqueous solution as a mobile phase at a flow rate of 1.0 mL/min. The eluent was monitored at 230 nm, and the resulted retention times of TXL and IS were 11.2 and 20.4 min. The detection limits of TXL for human plasma, serum and rat plasma samples at a signal-to-noise ratio of 3 were 10, 9.5 and 7.5 ng/mL, respectively. The proposed methods were applicable to the determination of TXL in human patients' plasma ranging from 15 to 27 ng/mL. Furthermore, monitoring of the time course of TXL after its single administration to rat could be demonstrated.

Aged↗

PubMed2006

Determination of donepezil hydrochloride in human and rat plasma, blood and brain microdialysates by HPLC with a short C30 column.

A simple and sensitive HPLC method with fluorescence (FL) detection for determination of donepezil (DP) in plasma and microdialysate samples was developed. A rapid isocratic separation of DP could be achieved by a short C30 column using mobile phases of 25 mM citric acid/50 mM Na2HPO4 (pH 6.0)-CH3CN (73:27%, v/v) containing 3.5 mM sodium 1-octanesulfonate for plasma and H2O-CH3CN-CH3OH (80:17:3%, v/v/v) containing 0.01% acetic acid for microdialysate. The eluate was monitored at 390 nm with an excitation at 325 nm. The detection limits (S/N = 3) of DP for human plasma, rat plasma and rat brain or blood microdialysates were 0.2, 1.0 and 2.1 ng/ml, respectively. Reproducible results could be obtained by using (+/-)-2-[(1-benzyl-piperidine-4-yl)ethyl]-5,6-dimethoxyindan-1-one hydrochloride as an internal standard (IS). The method was successfully applied for monitoring of DP levels in rat plasma, blood and brain microdialysates and patient plasma.

Animals↗

PubMed2006

A simple and sensitive HPLC-fluorescence method for quantification of MDMA and MDA in blood with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl) as a label.

A sensitive high-performance liquid chromatographic method with fluorescence detection to determine 3,4-methylenedioxymethamphethamine (MDMA) and 3,4-methylenedioxyamphethamine (MDA) in human and rat whole blood or plasma samples was developed by using 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl) as a label. MDMA and MDA in a small amount of blood sample (ca 100 microL) were extracted by liquid-liquid extraction with ethyl acetate, and were derivatized with DIB-Cl under mild conditions (10 min at room temperature). A good separation of DIB-derivatives could be achieved within 45 min using a commercially available ODS column with an isocratic eluent of 10 mM citric acid-20 mM Na(2)HPO(4) aqueous buffer (pH 4.0)-CH(3)CN-CH(3)OH (50:45:5, v/v/v %). The calibration curves prepared with 1-methyl-3-phenylpropylamine (MPPA) as an internal standard showed good linearity (r = 0.999) with 0.36-0.83 ng/mL detection limit at a signal-to-noise ratio of 3. MDMA and MDA in rat whole blood could be monitored for 6 h after a single administration of MDMA (2.2 mg/kg, i.p.). The pharmacokinetic parameters for MDMA and MDA obtained by triplicate measurements were 426 +/- 23 and 39 +/- 6 ng/mL (C(max)), 20 +/- 5 and 100 +/- 10 min (T(max)), respectively.

3,4-Methylenedioxyamphetamine↗

PubMed2005

Capillary electrochromatography of caffeine and its metabolites in rat brain microdialysate.

A capillary electrochromatography (CEC) method has been developed for the separation of caffeine and its two metabolites 1-methylxanthine (1-MX) and 1,7-dimethylxanthine (1,7-DX). The stationary phase was 3-(1,8-naphthalimido) propyl-modified silyl silica gel (NAIP) and the best separations were achieved with 4.0 mM citrate buffer (pH 5.0) containing 80% methanol at an applied voltage of 25 kV. The compounds were completely separated in less than 3.5 min with good repeatability, which was approximately 3-times less than that in high-performance liquid chromatography (HPLC) with NAIP. The proposed method coupled with microdialysis was successfully applied to the monitoring of caffeine concentration in rat brain with detection limits of 1.11 microg/mL.

Animals↗

PubMed2004

Hair analysis for fenfluramine and norfenfluramine as biomarkers for N-nitrosofenfluramine ingestion.

In this paper, a high performance liquid chromatographic method with fluorescence detection (HPLC-FL) for the determination of fenfluramine (Fen) and norfenfluramine (Norf) in human hair as biomarker metabolites of N-nitrosofenfluramine (N-Fen) is described. Washed and cut hair segments were extracted by ultrasonication for 1h at room temperature in methanol. The extract was evaporated and applied for derivatization with the fluorescent reagent 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl). An HPLC-FL analysis was performed using an ODS column with mobile phase composition of acetonitrile and water (65:35, v/v) and monitored at 430 nm (excitation 325 nm). The method was sensitive with detection limits of 36 and 16 pg/mg hair for Fen and Norf, respectively. The linearity was assessed in the range 0.036-144 ng/mg for Fen and 0.016-127 ng/mg for Norf with correlation coefficients larger than 0.999. The method was successfully used for the segmental determination of Fen and Norf in hair samples obtained from hospitalized patients diagnosed with hepatotoxicity and suspected to ingest N-Fen. Both Fen and Norf could be detected in these patients' hair samples in the ranges 43-1389 pg/mg for Fen and 18-680 pg/mg for Norf and the results showed that the patients might ingest N-Fen for a period of not less than 5 months. As well, the method was applied for the determination of Fen and Norf in rats that possess pigmented and non-pigmented hair after an intraperitoneal administration of Fen. Both compounds were determined in black as well as in white hair.

Animals↗

PubMed2004

High performance liquid chromatography with fluorescence detection for the determination of phenylpropanolamine in human plasma and rat's blood and brain microdialysates using DIB-Cl as a label.

A high performance liquid chromatographic method for the determination of phenylpropanolamine (PPA) in human plasma and rat's brain and blood microdialysates using fluorescence (FL) detection after precolumn derivatization with 4-(4,5-diphenyl-1H-imidazole-2-yl)benzoyl chloride (DIB-Cl) is described. PPA was extracted from plasma samples by a liquid-liquid extraction method with ethyl acetate followed by derivatization with DIB-Cl, while the blood and brain microdialysates were directly subjected for derivatization. The DIB-derivatives of PPA and the internal standard, ephedrine (EP), were then separated using an isocratic HPLC-FL set at excitation and emission wavelengths of 325 and 430 nm, respectively, on an ODS column. Calibration curves of PPA in spiked human plasma were linear over the concentration range of 5-5000 nM (0.755-755 ng/ml) and those in spiked blood and brain microdialysates were linear over the range of 25-5000 nM (3.775-755 ng/ml) with limits of detection of 17, 48 and 40 fmol on column in plasma and blood and brain microdialysates, respectively. As well, the intra- and the inter-assay precisions were lower than 12% for human plasma and the microdialysates. The method was successfully applied for the monitoring of PPA levels in rat's brain and blood microdialysates administered with a single oral dose of PPA (2.5 mg/kg).

Animals↗

PubMed2004

Decrease in serotonin concentration in raphe magnus nucleus and attenuation of morphine analgesia in two mice models of neuropathic pain.

The alleviation of neuropathic pain cannot be satisfactorily achieved by treatment with opioids. There is much evidence to indicate that the active site of morphine for inducing effective analgesia is in the raphe magnus nucleus, where serotonin (5-HT, 5-hydroxytryptamine) acts as a primary transmitter. Therefore, we developed the hypothesis that 5-HT released in the raphe magnus nucleus could be related to the effectiveness of morphine in two mice models of neuropathic pain, diabetic (DM)-induced neuropathy and sciatic nerve ligation (SL). Two weeks after a single administration of streptozotocin, or 10 days after sciatic nerve ligation, mice were subcutaneously (s.c.) injected with morphine at 3, 5 and 10 mg/kg. The antinociceptive effect of morphine was estimated in the tail-pinch test; 5-HT content was measured after induction of neuropathic pain by microdialysis followed by high-performance liquid chromatography with electrochemical detection (HPLC-ECD). Morphine produced as insufficient antinociceptive effect in SL mice at all doses compared with that in sham-operated mice, while in DM mice, morphine given s.c. at 5 and 10 mg/kg produced antinociceptive effects compared with those in non-diabetic mice, but not at 3 mg/kg. The 5-HT content of dialysates, expressed as AUC for 75 min, in SL and DM mice was less than that in control mice. However, morphine given s.c. at 5 mg/kg did not significantly affect 5-HT levels in both mice models compared to their controls. These results suggest that the decrease in 5-HT levels in the raphe magnus nucleus may be related to attenuation of the analgesic effect of morphine caused by the abnormal pain state found in diabetes and partial peripheral nerve injury.

Analgesics, Opioid↗

PubMed2004

Pharmacokinetic interactions between phenylpropanolamine, caffeine and chlorpheniramine in rats.

As the mechanism involved in the serious adverse effects associated with phenylpropanolamine (PPA) has not yet been clarified, and as PPA in usual cases is not being ingested without other drugs combination, the aim of this study was to characterize the possibility of pharmacokinetic interactions between PPA and most often combined drugs existing in the same dosage. The pharmacokinetics of PPA in rat brain and blood were evaluated when administered alone (group I), combined with caffeine (group II), combined with chlorpheniramine (group III), combined with both caffeine and chlorpheniramine (group IV) and finally when existed in one of the available OTC products (group V). This product contains multiple ingredients of PPA, caffeine and chlorpheniramine. In brain the pharmacokinetic parameters of PPA were significantly affected with the combined administration of caffeine and/or chlorpheniramine. The single intraperitoneal administration of caffeine (5 mg/kg) with PPA (2.5 mg/kg) to rats caused 1.6-fold increase in the AUC of PPA in brain compared to the single administration of PPA, and was comparable to the 1.5-fold increase caused by chlorpheniramine (0.4 mg/kg). The multiple combinations caused an increase in the AUC by 1.9-fold, which is comparable to the increase in the AUC of PPA obtained from the OTC product (2.2-fold). On the other hand, there was no significant difference in the pharmacokinetics of PPA in blood between the groups except for the C(max) of PPA in groups I and IV. The observed adverse effects associated with PPA use could be related to the significant increase in its levels in the brain.

Animals↗

PubMed2004

Disability of development of tolerance to morphine and U-50,488H, a selective kappa-opioid receptor agonist, in neuropathic pain model mice.

We examined the analgesic and anti-allodynic effects of morphine and U-50,488H (trans-(+/-)-3,4-dichloro-N-methyl-N-(2-[1-pyrrolidinyl]-cyclohexyl)-benzeneacetamide methanesulfonate salt), a selective kappa-opioid receptor agonist, and the development of tolerance to their effects in neuropathic pain model mice induced by sciatic nerve ligation (SNL). In the tail-pinch method, morphine at 10 mg/kg, s.c. produced a weak analgesic effect in SNL mice; however, U-50,488H at 5 mg/kg, s.c. produced an analgesic effect equipotent to that in normal mice. In contrast, morphine produced an adequate analgesic effect when given either intracerebroventricularly (i.c.v.) or intrathecally (i.t.), but U-50,488H only produced analgesia when given i.t. Repeated administration of morphine (either i.c.v. or i.t.) or U-50,488H (either s.c. or i.t.), did not induce tolerance to the effect. In the static allodynia test with an application of von Frey filaments, both compounds given s.c. suppressed the allodynic effect, but in the dynamic allodynia test involving lightly stroking the plantar surface with a cotton bud, only U-50,488H produced an anti-allodynic effect. Repeated administrations of both compounds did not develop tolerance to these anti-allodynic effects. Thus, U-50,488H was found to be a highly effective at blocking hyperalgesia and allodynia in nerve injury, and these findings suggest that kappa-opioid receptor agonists are attractive pharmacological targets for the control of patients with neuropathic pain.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed2003

Liquid chromatography studies on the pharmacokinetics of phentermine and fenfluramine in brain and blood microdialysates after intraperitoneal administration to rats.

A highly sensitive and simple HPLC method with fluorescence detection for the determination of phentermine (Phen), fenfluramine (Fen) and norfenfluramine (Norf, the active metabolite of Fen) in rat brain and blood microdialysates has been developed. The brain and blood microdialysates were directly subjected to derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl) benzoyl chloride (DIB-Cl) in the presence of carbonate buffer (0.1 M, pH 9.0) at room temperature. The chromatographic conditions consisted of an ODS column and mobile phase composition of acetonitrile and water (65:35, v/v) with flow rate set at 1.0 ml/min. The detection was performed at excitation and emission wavelengths of 325 and 430 nm, respectively. Under these conditions, the DIB-derivatives of Phen, Fen and Norf were well separated and showed good linearities in the studied ranges (5-2000 nM for Phen and 10-2000 nM for Norf and Fen) with correlation coefficients greater than 0.999. The obtained detection limits were less than 23 fmol on column (for the three compounds) in both brain and blood microdialysates at a signal-to-noise ratio of 3 (S/N=3). The intra- and the inter-assay precisions were lower than 10%. The method coupled with microdialysis was applied for a pharmacokinetic drug-drug interaction study of Phen and Fen following individual and combined intraperitoneal administration to rats. In addition, since the role of protein binding in drug interactions can be quite involved, the method was applied for the determination of total and free Phen and Fen in rat plasma and ultrafiltrate, respectively. The results showed that Fen and/or Norf significantly altered the pharmacokinetic parameters of Phen in both blood and brain but did not alter its protein binding. On the other hand, there was no significant difference in the pharmacokinetics of Fen when administered with Phen.

Animals↗

PubMed2003

Semi-micro column HPLC of triazolam in rat plasma and brain microdialysate and its application to drug interaction study with itraconazole.

Semi-micro column high-performance liquid chromatographic method with ultraviolet detection for the determination of triazolam (TZ) in rat plasma and brain microdialysate is described. The separation was achieved on a 250 x 1.5 mm, i.d. C(18) column and the column effluent was monitored at 222 nm. The detection limits at a signal-to-noise ratio of 3 obtained using spiked plasma and artificial cerebrospinal fluid were 2.1 and 0.7 ng/ml, respectively. The method was applied to drug-drug interaction study of TZ with itraconazole (ITZ). The peak concentration (C(max)) and the area under the curve (AUC) of TZ in brain microdialysate after simultaneous administration of TZ (2.5 mg/kg, intravenously (i.v.)) and ITZ (25 mg/kg, p.o.) to rats increased 3.4-folds (P<0.001) and 2.9-folds (P<0.001), respectively, compared to those of TZ alone. Also, the AUC of TZ in plasma increased 2.6-folds and remarkable delay in its elimination half-life (t(1/2)) was observed. The concentrations of TZ in brain microdialysate and plasma were also measured after single administration of TZ (2.5 mg/kg, i.v.) to rats pretreated with daily administration of ITZ (25 mg/kg, p.o.) once a day for a week. There was no significant difference in TZ's C(max) in both ITZ treatments (P>0.2) however its t(1/2) after the daily pretreatment with ITZ was significantly increased (P<0.05). In plasma, the AUC of TZ after daily pretreatment of ITZ was lower than the single combined treatment, but significantly different from TZ's AUC in the absence of ITZ (P<0.05). As a result, single simultaneous administration of TZ with ITZ and single administration of TZ after daily pretreatment with ITZ to rats, ITZ seriously interfered with the pharmacokinetic parameters of TZ in plasma and brain micodialysate.

Animals↗

PubMed2003

Simultaneous determination of arylpropionic acidic non-steroidal anti-inflammatory drugs in pharmaceutical formulations and human plasma by HPLC with UV detection.

A simple and sensitive high-performance liquid chromatography-UV detection method was developed for the simultaneous determination of non-steroidal anti-inflammatory drugs (NSAIDs) having an arylpropionic acid moiety in pharmaceutical formulations and human plasma. Isocratic separation was employed on ODS column (250 x 4.6 mm i.d., 5 microm) at ambient temperature. The mobile phase consisted of acetonitrile, phosphate buffer (pH 3.5; 50 mM), methanol and tetrahydrofuran. The NSAIDs in the eluent were monitored under a wavelength-programme to provide their maximum absorbance. Mefenamic acid was used as an internal standard. Drugs were found to be 96.8-101.9% of their label claim in pharmaceutical formulations. One hundred microliters of human plasma samples were pretreated with a simple liquid-liquid extraction using ethyl acetate. The detection limits of compounds studied at a signal-to-noise ratio of 3 were 11.5-75 ng/ml in human plasma samples. The proposed method is simple, selective and could be applicable for routine analysis of arylpropionic acidic NSAIDs in pharmaceutical as well as in human plasma samples.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2003

Possible role of nitric oxide in anxiety following transient cerebral ischemia in mice.

The possible role of nitric oxide (NO) in anxiety following transient cerebral ischemia by a 10-min bilateral carotid occlusion was examined in mice. Two days after the ischemia, mice showed a significant decrease in time spent on the open arms in the elevated plus-maze test; and likewise, they showed shortened social interaction time in the social interaction test, suggesting the induction of anxiety. Such anxiety behavior, however, was diminished 7 days after the treatment in both tests. A nonselective nitric oxide synthase (NOS) inhibitor, N( omega)-nitro-L-arginine methyl ester (L-NAME), and a selective inducible NOS (iNOS) inhibitor, S-ethylisothiourea (EIT), given twice after reperfusion, produced an anxiolytic effect in the elevated plus-maze test 2 days after the ischemia, while only the former produced antianxiety in the social interaction test. A relatively selective neuronal NOS (nNOS) inhibitor, 7-nitroindazole (7-NI), failed to decrease the level of anxiety in both tests. These results suggest that the production of NO participates in the anxiogenic behavior by the ischemia. Furthermore, NO generated by endothelial NOS (eNOS) or eNOS with iNOS, with no involvement of nNOS, plays an important role in the anxiety induced by the ischemia. Thus, we conclude that 10-min bilateral carotid occlusion provides a useful exploratory animal model for anxiety following transient cerebral ischemia.

Animals↗

PubMed2002

Disposition of triazolam in the rat by brain microdialysis and semi-micro column high-performance liquid chromatography with UV absorbance detection.

A semi-micro column high-performance liquid chromatography with ultraviolet detection for the determination of triazolam is described. The method was applied to determine plasma and brain microdialysate concentrations of triazolam after single intravenous bolus of 2.5 mg/kg to rat. The separation was achieved on a 250 x 1.5 mm i.d. C(18) column and the column effluent was monitored at 222 nm. The detection limits at a signal-to-noise ratio of 3 obtained using spiked plasma and artificial cerebrospinal fluid were 2.1 and 0.7 ng/mL, respectively. The intra- and inter-day reproducibility of the present method were satisfactory with the highest relative standard deviation of 9.1 (n > or = 5). The present method was successfully applied to study the disposition of triazolam in rat (n = 5) by analyzing plasma and brain microdialysate samples.

Animals↗

PubMed2002

Determination of bisphenol A in rat brain by microdialysis and column switching high-performance liquid chromatography with fluorescence detection.

A sensitive column switching HPLC-fluorescence detection for determination of bisphenol A (BPA) in rat brain by coupling with microdialysis was developed. A microdialysis probe was inserted into the hypothalamus of rat brain and an artificial cerebrospinal fluid was used for perfusion. BPA in brain dialysate was subjected to a fluorescent derivatization with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl), and the excess reagent was removed by a column-switching technique. Separation was carried out on two ODS semimicro-columns with the mobile phase of acetonitrile-H(2)O-methanol-tetrahydrofuran (55:10:35:2.5, v/v) and acetonitrile-0.1 M acetate buffer (pH 3.0)-methanol (35:10:55, v/v) at a flow rate of 0.10 and 0.15 mL/min for a precolumn and a separation column, respectively. Fluorescence intensity was monitored at 475 nm with excitation of 350 nm. BPA could be sensitively detected at 0.3 ppb in 60 micro L brain microdialysate at a signal-to-noise ratio of 3. By the proposed method, concentrations of BPA in rat brain and plasma were monitored for 8 h after single i.v. or oral administration. It is proved that BPA is capable of penetrating the blood-brain barrier. The ratio of the area under the concentration-time curve of BPA in rat brain to that in blood was estimated to be about 3.0-3.8%.

Animals↗

PubMedDate not supplied

Determination of MDMA and MDA in rat urine by semi-micro column HPLC-fluorescence detection with DBD-F and their monitoring after MDMA administration to rat.

A simultaneous semi-micro column HPLC method with fluorescence detection of abused drugs, such as 3,4-methylenedioxymethamphetamine (MDMA), 3,4-methylenedioxyamphetamine (MDA), amphetamine (AP) and methamphetamine (MP) in rat urine was examined by using 4-(N,N-dimethylaminosulphonyl)-7-fluoro-1,2,3-benzoxadiazole (DBD-F) as a labelling reagent and alpha-phenylethylamine as an internal standard (IS). A sample (50 microL) of rat urine was added to 5 microL IS and 100 microL 100 mmol/L borate buffer (pH 12) and extracted with 1.5 mL n-hexane. After evaporation, 50 microL 75 mmol/L borate buffer (pH 8.5) and 50 microL 20 mmol/L DBD-F in CH3CN were added to the residue and mixed well. The resultant solution was heated for 20 min at 80 degrees C and then cooled in an ice bath. A good separation of DBD-derivatives could be achieved within 45 min using a semi-micro ODS column with an eluent of CH3CN/CH3OH/10 mmol/L imidazole-HNO3 buffer (pH 7.0) (= 45:5:50, v/v/v %). The DBD derivatives were monitored at 565 nm with an excitation at 470 nm. The calibration curves showed good linearity (r = 0.997) with 0.5-15 ng/mL detection limits at a S/N ratio of 3. MDMA and MDA in rat urine could be monitored for 15 h after a single administration of MDMA to rat (2.0 mg/kg, i.p.). The concentrations for MDMA and MDA (n = 3) were 0.13-160.1 and 0.17-10.9 microg/mL, respectively.

3,4-Methylenedioxyamphetamine↗

PubMedDate not supplied

Pentazocine monitoring in rat hair and plasma by HPLC-fluorescence detection with DIB-Cl as a labelling reagent.

Pentazocine (PZ) in rat hair and plasma was determined by HPLC-fluorescence detection with 4-(4,5-diphenyl-1H-imidazol-2-yl)benzoyl chloride (DIB-Cl) as a labelling reagent and cyclazocine (CZ) as an internal standard (IS). PZ and IS extracted from hair or plasma sample were derivatized with DIB-Cl and the resulted solution was cleaned up with solid phase extraction. The isocratic separation of DIB-PZ and -CZ within 20 min could be achieved by a Wakopak Handy-ODS column (250 x 4.6 mm i.d.) using a mobile phase composed of 0.1 mol/L acetate buffer (pH 6.2):acetonitrile (25:75, v/v). The detection limits of PZ at a signal-to-noise ratio of 3 for rat hair and plasma were 0.18 ng/mg and 0.57 ng/mL, respectively. Reproducible and precise results could be obtained by an IS method with RSD values less than 6.6% for within- and between-day measurements. The method was successfully applied for the monitoring of PZ levels in Zucker rat hair and plasma samples after a single administration of 25 mg/kg PZ. Moreover, incorporation rates of PZ into black and white hair of Zucker rat were evaluated.

Animals↗