Tetsuya Saita

Sojo University, Kumamoto, Kumamoto, Japan

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Publications (40)96.35 Total impact

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    ABSTRACT: The multikinase inhibitor sorafenib has been used in the treatment of hepatocellular carcinoma, renal cell carcinoma, and differentiated thyroid carcinoma. Here we have demonstrated the production of the first specific antibody against sorafenib. Anti-sorafenib serum was obtained by immunizing mice with an antigen conjugated with bovine serum albumin and carboxylic modified 4-(4-aminophenoxy)-N-methyl-2-pyridinecarboxamide (AMPC) using the N-succinimidyl ester method. Enzyme labeling of sorafenib with horseradish peroxidase was similarly performed using carboxylic modified AMPC. A simple competitive enzyme-linked immunosorbent assay (ELISA) for sorafenib was developed using the principle of direct competition between sorafenib and the enzyme marker for anti-sorafenib antibody, which had been adsorbed by the plastic surface of a microtiter plate. Serum sorafenib concentrations lower than 0.04 μg/mL were reproducibly measurable using the ELISA. This ELISA was specific to sorafenib and showed very slight cross-reactivity (2.5%) with a major metabolite, sorafenib N-oxide. The values of serum sorafenib levels from 32 patients measured by this ELISA were comparable with those measured by HPLC, and there was a strong correlation between the values determined by the two methods (Y=1.016X-0.137, r=0.979). The specificity and sensitivity of the ELISA for sorafenib should provide a valuable new tool for use in therapeutic drug monitoring and pharmacokinetic studies of sorafenib.
    Full-text · Article · Nov 2015 · Biological & Pharmaceutical Bulletin
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    Tetsuya Saita · Yuta Yamamoto · Masashi Shin · Yukitaka Nakano
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    ABSTRACT: In this paper, we describe the production of the first specific antibodies against the tyrosine kinase inhibitors lapatinib and nilotinib. Anti-lapatinib antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin using 3-chloro-4-((3-fluorobenzyl)oxy)aniline. Anti-nilotinib antibody was produced by immunizing mice with an antigen conjugated with bovine serum albumin using 2-(5-amino- 2-methylanilino)-4-(3-pyridyl)pyrimidine. The generated antibodies were used to develop highly sensitive and specific enzyme-linked immunosorbent assays (ELISAs) for lapatinib and nilotinib in human serum. The assays were capable of detecting lapatinib and nilotinib at serum concentrations as low as 40 and 8 ng/mL, respectively. Using the two ELISAs, drugs levels were easily measured in the serum of rats after a single dose oral administration of lapatinib or nilotinib. The assays are therefore expected be valuable tools for therapeutic drug monitoring in the clinical setting and pharmacokinetic studies of lapatinib and nilotinib.
    Preview · Article · Oct 2015 · Biological & Pharmaceutical Bulletin
  • Tetsuya Saita · Masashi Shin · Hiroshi Fujito
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    ABSTRACT: Imatinib is an oral tyrosine kinase inhibitor used for first-line treatment of chronic myeloid leukemia. Therapeutic drug monitoring targeting trough plasma levels of about 1000 ng/mL may help to optimize imantinib's therapeutic effect. This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for a pharmacokinetic evaluation of imatinib. Anti-imatinib antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin and succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. Enzyme labeling of imatinib with horseradish peroxidase was similarly performed using succinimidyl 4-{(4-methyl-1-piperazinyl)methyl}-benzoate. A simple ELISA for imatinib was developed using the principle of direct competition between imatinib and the enzyme marker for anti-imatinib antibody which had been adsorbed by the plastic surface of a microtiter plate. Serum imatinib concentrations lower than 40 pg/mL were reproducibly measurable using the ELISA. This ELISA was specific to imatinib and showed very slight cross-reactivity (1.2%) with a major metabolite, N-desmethyl imatinib. Using this assay, drug levels were easily measured in the blood of mice after their oral administration of imatinib at a single dose of 50 mg/kg. The specificity and sensitivity of the ELISA for imatinib should provide a valuable new tool for use in therapeutic drug monitoring and pharmacokinetic studies of imatinib.
    No preview · Article · Dec 2013 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: Recently, six furanocoumarin derivatives isolated from grapefruit juice were found to be inhibitors of CYP3A4, suggesting that they may be clinically active and useful constituents. We succeeded in developing a sensitive and specific enzyme-linked immunosorbent assay (ELISA) for these furanocoumarin derivatives in grapefruit juice.In this study, we examined the correlation between immunoactivity as indicated by ELISA and CYP3A4 inhibitory effects, in order to determine whether ELISA is a useful method for analysis of the CYP3A4-inhibitory activity of furanocoumarin derivatives. Our results show a close correlation between the values. Therefore, our findings strongly indicate that ELISA is a useful method for analysis of these furanocoumarins.Using this ELISA, grapefruit-derived products (grapefruit juice, jam and marmalade) were examined for furanocoumarin derivatives. Immunoactivity analysis was used to determine the amount of 6',7'-dihydroxybergamottin conversion. The amount of 6',7'-dihydroxybergamottin conversion was 13.0 μg/g with grapefruit juice, 40.0 μg/g with grapefruit marmalade and 1.7 μg/g with grapefruit jam. In addition, it was found that the heat treatment of grapefruit juice decreases the immunoactivity as indicated by ELISA and the CYP3A4-inhibitory activity. Moreover, the decreasing rate of the CYP3A4-inhibitory activity was lower than that of the immunoactivity as indicated by ELISA. Therefore, when the heat-treating grapefruit-derived products were analyzed by the ELISA, it was suggested that the CYP3A4-inhibitory activity might be estimated low. These findings will become indexes of the drug interaction of grapefruit-derived products.
    Preview · Article · Jan 2013
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    ABSTRACT: We prepared monoclonal antibodies against N-(γ-maleimidobutyryloxy)succinimide-conjugated vancomycin (VM). The monoclonal antibody was specific for conjugated or free VM. The monoclonal antibody enabled us to develop an immunocytochemical method for detecting the uptake of VM in the rat kidney and liver. Three hours after a single intravenous (i.v.) injection of VM at the therapeutic dose, the immunocytochemistry revealed that VM accumulated in large amounts in both the S1 and S2 segments and in much smaller amounts in the S3 segment of the proximal tubules as well as in the distal tubules and collecting ducts. The drug was detected in the cytoplasm, cytoplasmic irregular granules, nuclei, and microvilli of the proximal tubule cells. The distal tubules and collecting ducts contained scattered swollen cells in which both the nuclei and cytoplasm were heavily immunostained. Twenty-four hours after injection, most of the swollen cells returned back to normal size and had somewhat decreased immunostaining. Also, significant amounts of VM remained accumulated for as long as 8 days postadministration. In the liver, similar drug accumulation was observed in the Kupffer cells and the endothelial cells of the hepatic sinusoids but not in the hepatocytes, suggesting that vancomycin cannot be eliminated via the liver. Immunoelectron microscopic studies demonstrated that in the collecting ducts, uptake of VM occurred exclusively in the lysosomes and cytoplasm of the principal cells and scarcely in the intercalated cells. Furthermore, double fluorescence staining using rats simultaneously administered with VM and gentamicin strongly suggests that both drugs colocalized in lysosomes in the proximal tubule cells of kidneys.
    Preview · Article · Sep 2012 · Antimicrobial Agents and Chemotherapy
  • Yukitaka Nakano · Tetsuya Saita · Hiroshi Fujito
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    ABSTRACT: This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for pharmacokinetic studies of vindesine (VDS). Anti-VDS antibody was obtained by immunizing rabbits with VDS conjugated with bovine serum albumin using N-[β-(4-diazophenyl) ethyl] maleimide as a heterobifunctional coupling agent. An enzyme marker was similarly prepared by coupling VDS with horseradish peroxidase using N-(4-diazophenyl) maleimide. The detection limit of VDS by ELISA was approximately 24 pg/mL with 50-mL samples. This assay was specific for VDS and showed very slight cross-reactivity with other vinca alkaloids, vincristine (0.18%) and vinblastine (0.11%). The values for the VDS concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, ELISA was about 50-fold more sensitive in detecting VDS at lower concentrations. The sensitivity and specificity of ELISA should provide a useful tool for pharmacokinetic studies of VDS.
    No preview · Article · Jun 2012 · YAKUGAKU ZASSHI
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    ABSTRACT: An in vivo role of the multidrug resistant-associated protein (Mrp2) in rat hepatocytes was examined by immunocytochemistry (ICC) for amoxicillin (AMPC) by the use of the transporter-deficient Eisai hyperbilirubinemic rats (EHBR). The ICC revealed that in the liver of EHBR at 3-h post-administration, amoxicillin accumulated in the cytoplasmic pools and nuclei of the hepatocytes in a characteristic granular morphology on the bile capillaries. However, no amoxicillin was observed on the surface of the lumina ranging from the bile capillaries to the interlobular bile ducts. The drug persisted at least for 6-h after administration. In contrast, in the control rat liver at 3-h post-administration, AMPC-adsorption occurred on such luminal surface, while AMPC accumulated to a less level in both the cytoplasm and nuclei of the hepatocytes. The drug completely disappeared in the hepatocytes at 6-h post-administration. These results strongly suggest that AMPC taken up into the cytoplasm of the hepatocytes excretes via Mrp2 into the bile flow. Furthermore, electron microscopy demonstrated that the lower electron density areas in large sizes, corresponding to the cytoplasmic pools in ICC for AMPC, occurred in the cytoplasm peripheral to the nuclei of the hepatocytes in EHBR at 3-h post-administration, and then disappeared 24 h after administration.
    No preview · Article · Mar 2012 · Journal of molecular histology
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    ABSTRACT: The in vivo role of transporters in drug disposition, in the context of other transporters, and metabolism has not been established. We prepared an anti-bestatin serum against bestatin conjugated to albumin with glutaraldehyde (GA). The antiserum was specific for GA-conjugated bestatin and weakly reacted with free bestatin, but no reaction occurred with structurally unrelated compounds according to both the inhibition and binding ELISAs. The antiserum allowed us to develop an immunocytochemical (ICC) method for detecting the uptake of bestatin in the rat intestine and kidney. Three hours after a single oral administration of bestatin, the ICC method revealed that the drug distributed in the microvilli, cytoplasm and nuclei of the absorptive epithelial cells at much larger amounts than in all other cell types in the small intestine. However, no drug was detected in the mucin goblets in the epithelium. In the kidney, the drug distributed to a greater extent in the S3 segment than in the S1 and S2 segments of the proximal tubule, and also was detected in the microvilli of the proximal tubule cells (S1, S2 and S3). These findings that bestatin accumulated in large amounts, especially in the cells and/or at the sites where the transporters PEPT1 and PEPT2 occur, corresponded well to those observed with β-lactam amoxicillin in the previous ICC studies. Thus, this may indicate a possibility that both the transporters might be involved, at least in part, in the distribution of bestatin in the small intestine and kidney under the conditions examined.
    No preview · Article · Dec 2011 · Journal of molecular histology
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    ABSTRACT: Peplomycin (PEP), an anti-tumor antibiotic related structurally to bleomycin, is widely used, especially for squamous cell carcinoma but shows renal toxicity. We prepared monoclonal antibodies (mAbs) against N-(γ-maleimidobutyryloxy)succinimide-conjugated PEP. The mAbs were monospecific for PEP, but did not react with bleomycin and other anticancer antibiotics. The mAbs enabled us to develop an immunocytochemical (ICC) method for detecting the uptake of PEP in the rat kidney. Two hours after a single i.v. administration of PEP, ICC revealed immunostaining for PEP in irregularly shaped cytoplasmic granules of the proximal tubules in which the microvilli were also stained. Also, staining occurred in the distal tubules and collecting ducts, in both of which we observed scattered swollen cells, reminiscent of necrotic cells, in which both the nuclei and cytoplasm reacted strongly with the antibody. Twenty-four hours after injection, PEP in the proximal tubules completely vanished, but yet significant amounts of PEP remained in both the distal tubules and collecting ducts. Distribution patterns of PEP in cells of the kidneys resembled, in some ways, those of our recent ICC studies for an organic cation aminoglycoside antibiotic gentamicin. This ICC suggests that PEP taken up in the proximal tubule cells is localized in the lysosomes, and organic cation transporters and bleomycin hydrolase might be involved in entrance and/or disappearance of PEP in this cell type. Furthermore, the distal tubules and collecting ducts may be the sites readily affected by some chemotherapeutic agents.
    No preview · Article · Jan 2011 · Histochemie
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    ABSTRACT: Gentamicin (GM) is a widely used antibiotic but shows renal toxicity. We produced a serum against GM (anti-GM) conjugated to bovine serum albumin with N-(gamma-maleimidobutyryloxy)succinimide. The antiserum was monospecific for GM and did not cross-react with the analog streptomycin, tobramycin, kanamycin, or amikacin. The antiserum also detected glutaraldehyde-fixed GM, and this enabled us to develop an immunocytochemical method for detecting the uptake of GM in rat kidney. Twelve hours after a single intravenous administration of GM, immunocytochemistry revealed that GM accumulated in the S1, S2, and S3 segments of the proximal tubules, as well as in the distal tubules and collecting ducts. By 12 h after injection, the drug was detected in cytoplasmic granules of the proximal tubule cells. However, early (1 h) after injection, drug accumulation was detected in the microvilli of these cells. The distal tubules and collecting ducts contained scattered swollen cells, reminiscent of necrotic cells, in which both the nuclei and the cytoplasm reacted strongly with GM. No staining occurred in the kidneys of saline-injected control rats. These results agree with previous studies showing that GM is endocytosed in the proximal tubules and accumulates in lysosomes. Additionally, our results show that GM also accumulates in the distal tubules and collecting ducts. This was achieved by systematically varying the pretreatment conditions-an approach necessary for detecting GM in different subcellular compartments. This approach should be useful for accurately detecting the uptake and toxicity of the antibiotic in different tissues.
    Preview · Article · Jun 2009 · Antimicrobial Agents and Chemotherapy
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    ABSTRACT: We have developed an enzyme-linked immunosorbent assay (ELISA) suitable for routine monitoring of serum levels of cibenzoline. Anti-cibenzoline antibody was obtained by immunizing rabbits with cibenzoline conjugated with bovine serum albumin using N-(4-maleimidobutyryloxy)succinimide as a heterobifunctional coupling agent. An enzyme marker was prepared by coupling 2,2-diphenylethylamine with beta-D-galactosidase using glutaraldehyde. The detection limit of cibenzoline by ELISA was approximately 640 pg/ml with 50-microl samples. Cross-reactivity data showed that the antibody well recognizes both the diphenyl and cyclopropyl moieties, and is thus specific enough to the structure of cibenzoline. The values for the cibenzoline concentrations detected using this assay were comparable with those detected using HPLC. There was a good correlation between the values determined by the two methods. Moreover, ELISA was about 15-fold more sensitive in detecting cibenzoline at lower concentrations. Using this assay, drug levels were easily measured in the serum of rabbits after oral administration of cibenzoline at a single dose of 3 mg/kg.
    No preview · Article · Jul 2007 · Yakugaku zasshi journal of the Pharmaceutical Society of Japan
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    ABSTRACT: Over the past several years, patients' safety has become a key issue for all health care institutions. In this regard, medication errors are a particularly serious matter because of their high frequency. We thought that Failure Modes and Effect Analysis (FMEA) would be an effective method of preventing them, since it can be used to evaluate each process systematically, and applied it to the risk management of a cancer chemotherapy medication system because patients suffer greatly in the case of medication errors in cancer chemotherapy.We collected inquiries concerning protocols and prescriptions from January to June 2005, and from them determined failure modes for the cancer chemotherapy medication system. The Risk Priority Number (RPN) for each failure mode was calculated by multiplying the severity of the effects of the failure by frequency and detectability, each given a rating of 1-3 (minimum 1 ; maximum 27).Among 187 protocols and 788 prescriptions, the frequencies of inquiry were 23.5% and 11.7%, respectively. Twenty-nine failure modes were isolated from the inquiries and the one with the highest RPN (15.9) was dosage errors in patients' chemotherapy protocols. Other high-ranking failure modes were errors in accumulated dosage, contraindications, administration schedules and laboratory data. Using the RPNs obtained, we created a hazard map for the cancer chemotherapy system.FMEA enabled us to numerically express the potential risks of the system and our findings suggest that it is essential to visualize and locate failures from every point of view of risk management in cancer chemotherapy.
    No preview · Article · Jan 2006
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    ABSTRACT: Information on drugs brought to hospital by inpatients is essential to the risk management of the treatment they receive after admission. In this regard, we investigated the effectiveness of a system under which a pharmacist checks the details of any drugs brought by inpatients on admission. A counter for this purpose was established in front of the inpatient reception desk and pharmacists were assigned to it to check any drugs brought by patients, the number of pharmacists depending on the time of admission and number of patients. The assignment of several pharmacists for 2-hour periods enabled us to check the drugs brought in by about 80% of the total number of inpatients. Information on drugs brought to hospital by patients was immediately input to the patients' medical database using a scanner to make it available for the use of physicians.
    No preview · Article · Jan 2006
  • Tetsuya Saita · Hiroshi Fujito · Masato Mori
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    ABSTRACT: The epidermal growth factor tyrosine kinase inhibitor gefitinib is a novel, molecularly targeted agent that has been approved for the treatment of advanced non-small cell lung cancer. This paper reports a specific and sensitive enzyme-linked immunosorbent assay (ELISA) for pharmacokinetic studies of gefitinib. Anti-gefitinib antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin using diazotized 4-amino-2-methoxy-1-[3-(morpholin-4-yl)propoxy]benzene. Enzyme labeling of gefitinib with beta-D-galactosidase was similarly performed using a diazotized 4-amino-2-methoxy-1-[3-(morpholin-4-yl)propoxy]benzene. A simple ELISA for gefitinib was developed using the principle of direct competition between gefitinib and the enzyme marker for anti-gefitinib antibody which had been adsorbed to the plastic surface of a microtiter plate. Gefitinib concentrations in serum lower than 800 pg/ml were measurable reproducibly using the ELISA. Cross-reactivity data showed that the antibody well recognizes both the 3-morpholinopropoxy and methoxy moieties well, and thus is sufficiently specific for the structure of gefitinib. Using this assay, drug levels were easily measured in the serum of rabbits after oral administration of gefitinib at a single dose of 5 mg/kg. The specificity and sensitivity of the ELISA for gefitinib should provide a valuable new tool for use in pharmacokinetic and toxicity studies of gefitinib.
    No preview · Article · Nov 2005 · Biological & Pharmaceutical Bulletin
  • Tetsuya Saita · Hiroshi Fujito · Masato Mori
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    ABSTRACT: This paper reports a sensitive and specific enzyme-linked immunosorbent assay for screening of furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in citrus fruits. Anti-6',7'-dihydroxybergamottin antibody was obtained by immunizing rabbits with 6',7'-dihydroxybergamottin conjugated with bovine serum albumin using the N-succinimidyl ester method. An enzyme marker was similarly prepared by coupling 6',7'-dihydroxybergamottin with beta-D-galactosidase. The enzyme-linked immunosorbent assay is capable of detecting as little as 800 pg/ml of 6',7'-dihydroxybergamottin and 4 ng/ml of bergamottin. Cross-reactivity data showed that the antibody well recognizes both the furanocoumarin and 6,7-dihydroxy-3,7-dimethyloct-2-enyloxy moieties of the 6',7'-dihydroxybergamottin, and is thus specific to the structure of furanocoumarin derivatives containing geranyloxy side chain as the cytochrome P450 3A4 inhibitors in grapefruit juice. The antibody was, therefore, used for screening a large number of citrus fruits for furanocoumarin derivatives such as 6',7'-dihydroxybergamottin. Fifteen citrus fruits were examined and significant reactivity was observed in 8 of these: red pummelo, sweetie, melogold, banpeiyu pummelo, hassaku, sour orange, lime and natsudaidai. This enzyme-linked immunosorbent assay may be a powerful tool for screening for furanocoumarin derivatives as cytochrome P450 3A4 inhibitors in grapefruit juice.
    No preview · Article · Aug 2004 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: A selective liquid chromatographic method has been developed for the assay of ethambutol in serum samples. The assay involves intramolecular excimer-forming derivatization with 4-(1-pyrene)butanoyl chloride (PBC) and isocratic reversed-phase chromatography with fluorescence detection. After acetonitrile-deproteinization of the serum sample, the derivatization reaction of ethambutol with PBC was completed within 30 min at 50 degrees C. N,N'-Diethylethylenediamine was used as an internal standard. The detection limit of ethambutol was 23 ng/ml serum, corresponding to 180 fmol on column at a signal-to-noise ratio of 3. The present method was selective enough to analyze ethambutol in rabbit serum without any tedious sample clean-up procedure because biogenic monoamines gave no peak in the chromatogram. The method was applicable to drug monitoring in rabbit serum.
    No preview · Article · Apr 2004 · Analytical Sciences
  • Tetsuya Saita · Hiroshi Fujito · Yukitaka Nakano · Masato Mori
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    ABSTRACT: We have established an enzyme-linked immunosorbent assay suitable for routine monitoring of serum levels of sotalol. Anti-sotalol antibody was obtained by immunizing rabbits with sotalol conjugated with bovine serum albumin using the N-succinimidyl ester method. An enzyme marker was similarly prepared by coupling sotalol with beta-D-galactosidase. The detection limit of sotalol by the enzyme-linked immunosorbent assay was approximately 32 ng/ml with 50-microl samples. This assay was specific for sotalol because of very slight cross-reactivity with 4-(methanesulfonylamino)benzonitrile (1.6%), but none with D,L-isoproterenol. Using this assay, drug levels were easily measured in the serum of rabbits after oral administration of sotalol at a single dose of 3 mg/kg. The enzyme-linked immunosorbent assay should be a valuable tool in therapeutic drug monitoring and pharmacokinetic studies of sotalol.
    No preview · Article · Feb 2004 · Biological & Pharmaceutical Bulletin
  • Tetsuya Saita · Hiroshi Fujito · Masato Mori
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    ABSTRACT: This paper reports a sensitive and specific enzyme-linked immunosorbent assay for determination of the antiarrhythmic drug mexiletine in human serum. Anti-mexiletine antibody was obtained by immunizing rabbits with an antigen conjugated with mercaptosuccinyl bovine serum albumin using N-(epsilon-maleimidocaproyloxy)succinimide as a heterobifunctional coupling agent. Enzyme labeling of mexiletine with beta-D-galactosidase was performed using glutaraldehyde. In this assay, the mexiletine to be quantified is chemically modified by acetic anhydride allowed to compete with a mexiletine-beta-D-galactosidase conjugate for binding to a limited amount of an anti-mexiletine antibody which was used to coat the wells of a microtiter plate. Mexiletine concentrations lower than 80 ng/ml were measurable reproducibly by the enzyme-linked immunosorbent assay. This assay was specific for mexiletine and showed very slight cross-reactivity with its major metabolite, 2-hydroxymethylmexiletine (1.5%), but none with p-hydroxymexiletine. The values of serum mexiletine levels from 15 patients by this enzyme-linked immunosorbent assay were comparable with those measured by HPLC. There was a good correlation between the values determined by the two methods. The enzyme-linked immunosorbent assay should be a valuable tool in therapeutic drug monitoring and pharmacokinetic studies of mexiletine.
    No preview · Article · Jul 2003 · Biological & Pharmaceutical Bulletin
  • Tetsuya Saita · Hiroshi Fujito · Masato Mori
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    ABSTRACT: A sensitive and specific enzyme-linked immunosorbent assay for an antiarrhythmic drug, amiodarone (AMI), was developed, which is capable of measuring levels as low as 16 ng/ml. Anti-AMI antibody was obtained by immunizing rabbits with an antigen conjugated with bovine serum albumin using diazotized 4-amino-1-(2-diethylaminoethoxy)-2,6-diiodobenzene. Enzyme labeling of AMI with beta-D-galactosidase was similarly performed using a diazotized 4-amino-1-(2-diethylaminoethoxy)-2,6-diiodobenzene. This enzyme-linked immunosorbent assay was specific for AMI and showed a very slight cross-reactivity (1.25%) with its major metabolite, mono-N-desethylamiodarone. The values of the AMI concentrations measured by this assay were in good correlation to those by HPLC. Its analytical applicability was demonstrated by a kinetic study with human liver microsomes. The enzyme-linked immunosorbent assay should be a valuable tool in therapeutic drug monitoring and pharmacokinetic studies of AMI.
    No preview · Article · Sep 2002 · Biological & Pharmaceutical Bulletin
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    ABSTRACT: A highly selective and simple fluorimetric liquid chromatographic method for the determination of triethylenetetramine (TETA), a therapeutic drug for Wilson's disease, in human and rabbit sera is described. This method is based on intramolecular excimer-forming fluorescence derivatization, which allows spectrofluorometric discrimination of polyamino compounds from monoamino species, followed by liquid chromatography. TETA and 1,6-hexanediamine (internal standard) were converted to the corresponding excimer-forming derivatives with a pyrene reagent, 4-(1-pyrene)butyric acid N-hydroxysuccinimide ester. The derivatives were separated within 20 min on a reversed-phase column using isocratic elution and detected spectofluorometrically at 480 nm with excitation at 345 nm. This method was successfully applied to the monitoring of TETA in human and rabbit sera with a simple pretreatment. The detection limit for TETA in serum was 18 ng/ml (0.13 nmol/ml) corresponding to 0.2 pmol on column at a signal-to-noise ratio of 3.
    No preview · Article · Aug 2002 · Journal of Chromatography B

Publication Stats

368 Citations
96.35 Total Impact Points

Institutions

  • 2012-2015
    • Sojo University
      • • Faculty of Biotechnology and Life Science
      • • Applied Life Science Department
      Kumamoto, Kumamoto, Japan
  • 2004-2012
    • Saga University
      Сага Япония, Saga, Japan
  • 2009
    • Daiichi College of Pharmaceutical Sciences
      Hukuoka, Fukuoka, Japan
  • 1986-1993
    • Nagasaki University
      • School of Medicine
      Nagasaki, Nagasaki, Japan