Measurement of Anti-Cancer Agent Methoxyamine in Plasma by Tandem Mass Spectrometry with On-Line Sample Extraction

In this work, we present the development and validation of a tandem mass spectrometry method for the quantitative determination of methoxyamine (CH3ONH2), a potential new chemotherapeutic agent, in human and mouse plasma. Methoxyamine together with the internal standard (I.S.) methoxyl-D3-amine was directly derivatized in plasma sample with a novel chemical agent 4-(N,N-diethylamino)benzaldehyde. The product solution was injected into an on-line Oasis® HLB extraction column ( mm) for analyte extraction. After the elution of extractives, the derivatized analytes were monitored by the positive-electrospray-ionization mass spectrometry (ESI-MS-MS). The structures of derivatized analytes were elucidated by fragmentation. Quantitation of plasma methoxyamine was carried out by the multiple reaction monitoring (MRM) mode. This method had a linear calibration range of 1.00–1000 ng/ml with a correlation coefficient of 0.9999 for methoxyamine in both human and mouse plasma. The limit of detection (LOD) and limit of quantification (LOQ) for methoxyamine in plasma were 0.150 and 0.500 ng/ml, respectively. It was demonstrated that the method had high recovery and accuracy (90.1–94.7 and 90.1–96.3%), as well as excellent intra- and inter-assay precision (2.2 and 3.7%), at three concentration levels (5.00, 50.0, 500 ng/ml). This method has been used to analyze the plasma levels of methoxyamine in samples obtained from male CD1 mice after bolus intraperitoneal injection of 2, 5 and 20 mg methoxyamine hydrochloride (CH3ONH2.HCl) per kilogram mouse

Indeks Kepuasan Pengguna Situs Web E-Gov di Bali dengan Metode EUCS dan CSI

Provinsi Bali memiliki 8 (delapan) situs web Pemerintah Kabupaten, 1 (satu) situs web Pemerintah Provinsi, dan 1 (satu) situs web pemerintah Kota. Akan tetapi pengelola dari masing – masing situs web e-gov tidak pernah melakukan pengukuran indeks kepuasan pengguna terhadap fasilitas layanan informasi yang ditampilkan pada situs web e-gov tersebut secara rutin. Pengukuran indeks kepuasan pengguna situs web e-gov secara nasional terakhir dilakukan oleh Kementrian Komunikasi dan Informatika (KOMINFO) pada ICT Pura tahun 2012. Untuk mengetahui tingkat kepuasan pengguna terhadap fasilitas layanan pada situs web e-gov Pemerintah di Provinsi Bali, penelitian ini menggunakan metode End-User Satisfaction Index (EUCS) dan Customer Satisfaction Index (CSI) untuk dapat mengetahui kategori web e-gov dalam suatu survei kepuasan dan memberikan rekomendasi perbaikan layanan informasi pada situs web e-gov masing –masing Pemerintah Daerah di Provinsi Bali. Hasil dari penelitian ini adalah indeks kepuasan pengguna situs web e-gov yang menempatkan situs web Kabupaten Klungkung (tertinggi) dan situs web e-gov Kabupaten Tabanan (terendah)

Mobilization of mercury from lean tissues during simulated migratory fasting in a model songbird

The pollutant methylmercury accumulates within lean tissues of birds and other animals. Migrating birds catabolize substantial amounts of lean tissue during flight which may mobilize methylmercury and increase circulating levels of this neurotoxin. As a model for a migrating songbird, we fasted zebra finches (Taeniopygia guttata) that had been dosed with 0.0, 0.1, and 0.6 parts per million (ppm) dietary methylmercury and measured changes in blood total mercury concentrations (THg) in relation to reductions in lean mass. Birds lost 6-16% of their lean mass during the fast, and THg increased an average of 12% and 11% in the 0.1 and 0.6 ppm treatments, respectively. Trace amounts of THg in the 0.0 ppm control group also increased as a result of fasting, but remained extremely low. THg increased 0.4 ppm for each gram of lean mass catabolized in the higher dose birds. Our findings indicate that methylmercury is mobilized from lean tissues during protein catabolism and results in acute increases in circulating concentrations. This is a previously undocumented potential threat to wild migratory birds, which may experience greater surges in circulating methylmercury than demonstrated here as a result of their greater reductions in lean mass

Development and Validation of An LC–MS/MS Method for Pharmacokinetic Study of Methoxyamine in Phase I Clinical Trial

Methoxyamine (MX) is the first DNA base-excision-repair (BER) inhibitor evaluated in humans. This work described the development and validation of an LC–MS/MS method for quantitative determination of MX in human plasma. In this method, MX and its stable isotope methoxyl-d3-amine (MX-d3 as internal standard) were directly derivatized in human plasma with 4-(N,N-diethylamino)benzaldehyde. The derivatized MX and IS were extracted by methyl-tert-butyl ether, and separated isocratically on a Xterra C18 column (2.1 mm × 100 mm) using an aqueous mobile phase containing 45% acetonitrile and 0.4% formic acid at a flow rate of 0.200 ml/min. Quantitation of MX was carried out by multiple-reaction-monitoring (MRM) mode of positive turbo-ion-spray tandem mass spectrometry. This method has been validated according to FDA guidelines for bioanalytical method. The linear calibration range for MX was 1.25–500 ng/ml in human plasma with a correlation coefficient ≥ 0.9993. The intra- and inter-assay precision (%CV) at three concentration levels (3.50, 45.0 and 450 ng/ml) ranged 0.9–1% and 0.8–3%, respectively. The stability studies showed that MX met the acceptable criteria under all tested conditions. The method developed had been applied to the determination of plasma MX concentrations in the first-in-human phase I clinical trial, and PK data were presented

Development and Validation of An LC–MS/MS Method for Pharmacokinetic Study of Methoxyamine in Phase I Clinical Trial

Methoxyamine (MX) is the first DNA base-excision-repair (BER) inhibitor evaluated in humans. This work described the development and validation of an LC–MS/MS method for quantitative determination of MX in human plasma. In this method, MX and its stable isotope methoxyl-d3-amine (MX-d3 as internal standard) were directly derivatized in human plasma with 4-(N,N-diethylamino)benzaldehyde. The derivatized MX and IS were extracted by methyl-tert-butyl ether, and separated isocratically on a Xterra C18 column (2.1 mm × 100 mm) using an aqueous mobile phase containing 45% acetonitrile and 0.4% formic acid at a flow rate of 0.200 ml/min. Quantitation of MX was carried out by multiple-reaction-monitoring (MRM) mode of positive turbo-ion-spray tandem mass spectrometry. This method has been validated according to FDA guidelines for bioanalytical method. The linear calibration range for MX was 1.25–500 ng/ml in human plasma with a correlation coefficient ≥ 0.9993. The intra- and inter-assay precision (%CV) at three concentration levels (3.50, 45.0 and 450 ng/ml) ranged 0.9–1% and 0.8–3%, respectively. The stability studies showed that MX met the acceptable criteria under all tested conditions. The method developed had been applied to the determination of plasma MX concentrations in the first-in-human phase I clinical trial, and PK data were presented

Photoconductivity Parameters In Lithium Niobate

Measurements on a variety of doped (magnesium and/or iron) and undoped lithium niobate crystals in the oxidized state demonstrate an Arrhenius dependence of dark conductivity on reciprocal temperature between 460 and 590 K. All of the crystals had roughly the same conductivity and activation energy (1.21 eV) over the temperature range, implying that all have about the same free-carrier concentration and mobility. The enhanced photoconductivity of magnesium-doped lithium niobate is attributed to a greatly reduced trapping cross section of Fe3+ for electrons, the smaller cross section being due to a changed substitutional site for Fe3+. The Fe3+ trapping cross section is calculated from photoconductivity data to be of order 10-18 m2 in undoped lithium niobate. This implies a photoelectron lifetime of order 6x10-11 s in a relatively pure (2-ppm Fe) oxidized crystal