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紀要委員会企画, Special Articles, 2022 年４月１日より保健師助産師看護師学校養成所指定規則の一部を改正した省令（厚生労働省，2019）が適応される。本規則の改正では、地域在宅看護の創設、実習単位が見直され、看護師に求められる社会的役割、及び疾病構造の変化に伴う療養生活の場の多様性に合わせた内容が示された。それに伴い、本学看護学部では本学の理念である生命の尊厳と隣人愛の精神を基盤として、2019 年よりカリキュラム改革を推進し検討を継続した。中長期ビジョン検討会、カリキュラム骨子作成委員会を経て、カリキュラム改革委員会が30 回を超える協議を重ね、新たなカリキュラムを申請するに至った。本稿では、新たなカリキュラムに至った経緯とカリキュラム編成の概要について報告する。

High-purity mullite ceramics, promising engineering ceramics for high-temperature applications, were fabricated using transient liquid phase sintering to improve their high-temperature mechanical properties. Small amounts of ultrafine alumina or silica powders were uniformly mixed with the mullite precursor depending on the silica-alumina ratio of the resulting ceramics to allow for the formation of a transient liquid phase during sintering, thus, enhancing densification at the early stage of sintering and mullite formation by the reaction between additional alumina and the residual glassy phase (mullitization) at the final stage of sintering. The addition of alumina powder to the silica-rich mullite precursor resulted in a reaction between the glassy silica and alumina phases during sintering, thereby forming a mullite phase without inhibiting densification. The addition of fine silica powder to the mullite single-phase precursor led to densification with an abnormal grain growth of mullite, whereas some of the added silica remained as a glassy phase after sintering. The resulting mullite ceramics prepared using different powder compositions showed different sintering behaviors, depending on the amount of alumina added. Upon selecting an optimum process and the amount of alumina to be added, the pure mullite ceramics obtained via transient liquid phase sintering exhibited high density (approximately 99%) and excellent high-temperature flexural strength (approximately 320 MPa) at 1500 °C in air. These results clearly demonstrate that pure mullite ceramics fabricated via transient liquid phase sintering with compositions close to those of stoichiometric mullite could be a promising process for the fabrication of high-temperature structural ceramics used in an ambient atmosphere. The transient liquid phase sintering process proposed in this study could be a powerful processing tool that allows for the preparation of superior high-temperature structural ceramics used in the ambient processing atmosphere.

B4C ceramics were fabricated by pressureless sintering, and the tribological behaviors of B4C ceramics without and with a postannealing treatment at different temperatures were investigated. It was...

A sensitive method was developed for the simultaneous determination of midazolam and propofol in human plasma samples via modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction for their analysis by gas chromatography–tandem mass spectrometry (GC–MS/MS). Detailed optimization and validation experiments were conducted; plasma quality control samples spiked with two drugs and two internal standards (ISs) were extracted using the QuEChERS technique and determined by GC–MS/MS. The present method was applied to the measurements in an actual clinical case. The regression equations for midazolam and propofol in plasma displayed good linearity (r > 0.9978) from 10 to 1000 ng/mL with a limit of quantification of 10 ng/mL. The intra- and interday precisions for both drugs were not greater than 8.6%. The accuracies of quantitation ranged from 98 to 110%. The extraction efficiencies of midazolam and propofol for plasma were 93 to 117%. The method was successfully applied to the analyses of plasma midazolam and propofol concentrations in a brain-injured patient subjected to hypothermia, which validated the present methodology. In this study, the authors have successfully established the detailed procedure for GC–MS/MS analysis of midazolam and propofol in human plasma. The sensitivity and specificity of the present method for the drugs were almost comparable to those by the standard liquid chromatography–tandem mass spectrometry. To their knowledge, this is the first report for analysis of midazolam/propofol by GC–MS/MS.

Purpose This study aims to investigate the friction behavior of SiC-B4C composite ceramics treated by annealing in air sliding against SiC balls. Design/methodology/approach The dry sliding tests were performed with a ball-on-disk tribometer in ambient air condition. Analysis of friction coefficient, phase compositions of the surfaces, morphologies of worn surfaces of disks and wear scars of balls and surface profiles of wear tracks for disks were carried out using Raman spectroscope, microscope and surface profilometer. Findings The results show that a self-lubricating layer with the main composition of H3BO3 was successfully fabricated on the surface of SiC-B4C composite ceramics by the annealing treatment in air. When the mass fraction of SiC is more than that of B4C, SiC-B4C composite ceramics show higher friction coefficients, the values of which are 0.38 for 80 Wt.%SiC-20 Wt.%B4C and 0.72 for 60 Wt.%SiC-40 Wt.%B4C, respectively. SiC-B4C composite ceramics show lower friction coefficients when the mass fraction of B4C is more than that of SiC. The low friction coefficients of 40 Wt.%SiC-60 Wt.% B4C composite ceramics (0.16) and 20 Wt.%SiC-80 Wt.% B4C composite ceramics (0.20) are attributed to the formation of a sufficient amount of H3BO3 layer, rather than the layer of silicon oxides. Originality/value This study will help to understand the friction behavior of SiC-B4C composite ceramics with different ratios of SiC to B4C treated by annealing in air.

The formation mechanisms of relief structure formed in situ on the surface of B4C–SiC ceramics were studied. The hardness difference between B4C and SiC is one of the formation conditions of relief structure. SiC grains are subjected to a preferential wearing owing to their lower hardness as compared to B4C grains, resulting in the difference of wear rates between B4C grains and SiC grains. Clean, no gap grain boundary in the B4C–SiC ceramics, which can make B4C grains and SiC grains bond firmly protecting them from pulling out, is another formation condition of relief structure.

Nanorelief structure formed on the surface of B4C–SiC ceramics by an in-situ method is reported. The nanorelief structure formed by the in-situ method, which differs from the relief structure produced by laser treatment, results from preferential wearing of SiC particles, which have lower hardness, by free diamond particles and mixed wear particles of B4C and SiC during polishing and sliding, respectively. The effect of the nanorelief structure formed by the in-situ method on the sliding dry friction against a SiC ball is examined using a pin-on-disk tribometer. A comparison of dry sliding of the B4C–SiC composite ceramics with nanorelief structure to that of SiC ceramics without nanorelief structure reveals that B4C–SiC composite ceramics have a lower coefficient of friction and a significantly lower specific wear rate than the SiC ceramics. Worn surface analysis indicates that the nanorelief structure does not disappear after a dry sliding test. The depth of the nanorelief structure formed by the in-situ method ranges from 10 to 40 nm. The friction and wear results are associated with the nanorelief structure formed by the in-situ method.

紀要委員会企画, Special Articles, 本稿は、本学看護学部の2019 年度教育課程改定における活動内容の概要を記した。2012 年に教育課程変更を行って５年が経過したことや、教育職員免許法の改正により養護教諭課程の再課程認定に伴い、2019 年度に向けて看護学部教育課程の改定を行うことになった。2017 年度からカリキュラム検討委員会を中心に教育課程の検討を行い、２年間に渡って教育課程改定に向けて活動した内容をまとめた。2019 年度新教育課程としては、地域包括ケアシステムの推進に基づく社会の変遷にあわせた教育課程へと発展させるための学修内容の追加、本学の強みである充実した実習環境をもとに行われている臨地看護学実習を通して「生命の尊厳と隣人愛」に基づく教育理念を継続的に意識づけられるような教育課程を策定することができた。指定規則改正に伴う次の教育課程の改定に向けて、今回のプロセスが参考となることを期待する。

Forensic toxicological analyses of drugs and their metabolites in human specimens usually require extractive pretreatment for successful analysis of substances from the matrix. In the present study, a high-throughput method was developed to analyze flunitrazepam, 7-aminoflunitrazepam, 7-acetamidoflunitrazepam, 7-acetamido-3-hydroxyflunitrazepam, and 3-hydroxyflunitrazepam in human plasma and urine samples using a new Monolithic C18 gel-packed SpinTip and ultra-performance liquid chromatography (UPLC)–quadrupole time-of-flight (Q-ToF) mass spectrometry (MS). Plasma (20 µL) or urine (100 µL) samples spiked with each component were extracted using a Monolithic C18 SPE SpinTip and quantified by UPLC–Q-Tof–MS with positive-ion electrospray ionization (ESI). Good separation, with clear peak shapes of flunitrazepam and its metabolites, was achieved within an analysis time of 6 min, including the extraction time. Recoveries of flunitrazepam and 7-aminoflunitrazepam for plasma and urine samples were 93.5–118% and 97.7–109%, respectively. The regression equations for flunitrazepam and 7-aminoflunitrazepam showed excellent linearity in the range of 0.5–250 ng/mL for plasma and 0.4–500 ng/mL for urine, with detection limits of 0.2–0.5 ng/mL. Intra- and inter-day coefficients of variations for two drugs are smaller than 13.5%. The accuracy of quantitation was 89–110%. The method was successfully applied to determine the level of flunitrazepam and its metabolites in human plasma and urine, respectively, after oral administration to a volunteer.

Aminoglycosides are a class of broad-spectrum antibiotics with several clinical uses. Owing to the ototoxicity and nephrotoxicity of aminoglycosides, therapeutic drug monitoring is required. This study aimed to devise a high-throughput method for identification and quantitative determination of aminoglycoside antibiotics in human plasma samples using ultra-performance liquid chromatography–quadrupole time-of-flight-mass spectrometry (UPLC–Q-ToF-MS). Plasma samples (100 µL) spiked with five aminoglycosides (streptomycin, spectinomycin, amikacin, kanamycin, and gentamycin) and an internal standard (ribostamycin) were diluted and centrifuged in aqueous formic acid and acetonitrile. The clear supernatant extract was evaporated and reconstituted in the mobile phase, of which 4 µL was subjected to UPLC–Q-ToF-MS. Prominent peaks were observed for the drugs within 3 min. The recoveries of five aminoglycosides from plasma samples were 92.6–120%. The regression equations showed excellent linearity (0.9999 ≥ r2 ≥ 0.9987) within the range of 1.0–100 µg/mL, and detection limits of 0.5–2.0 µg/mL. The coefficients of the intra- and inter-day variations for five drugs were less than 11.8%, while the accuracy of quantitation was in the range of 89–111%. In this study, a novel method was presented for identification and determination of aminoglycosides in human plasma samples using UPLC–Q-ToF-MS analysis. This method can be applied to high-throughput analysis used for clinical and environmental purposes.

A highly sensitive method was developed for the analysis of alendronate in human plasma and dialysate using MonoSpin™ SAX® extraction and metal-free high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS/MS) following methylation with trimethylsilyldiazomethane. The chromatographic separation of the derivatives for alendronate and alendronate-d6 was achieved on an L-column2 ODS metal-free column (50 mm × 2 mm i.d., particle size 3 µm) with a linear gradient elution system composed of 10 mM ammonium acetate (pH 6.8) and acetonitrile at a flow rate of 0.3 ml/min. Quantification was performed by multiple reaction monitoring (MRM) with positive-ion electrospray ionization (ESI). Distinct peaks were observed for alendronate and for the internal standard on each channel within 1 min. The regression equations showed good linearity within the ranges of 2.0-100 ng/0.5 ml for the plasma and 1.0-100 ng/0.5 ml for the dialysate, with the limits of detection at 1.0 ng/0.5 ml for the plasma and 0.5 ng/0.5 ml for the dialysate. Extraction efficiencies for alendronate for the plasma and dialysate were 41.1-51.2% and 63.6-73.4%, respectively. The coefficient of variation (CV) was ≤8.5%. The method was successfully applied to the analyses of real plasma and dialysate samples derived after intravenous administration of alendronate.

Rationale We developed a new high-throughput method to analyze tegafur (FT) and 5-fluorouracil (5-FU) in tear and plasma samples using hydrophilic interaction liquid chromatography (HILIC)/tandem mass spectrometry (MS/MS). Methods The tear samples (10 μL) spiked with FT, 5-FU, and 5-chlorouracil (internal standard) were diluted using 40 μL of 2 M ammonium acetate and 250 μL of acetonitrile with 2% formic acid; 20 μL of plasma spiked with the two drugs and internal standard was diluted with 80 μL of 2 M ammonium acetate and 500 μL of acetonitrile with 2% formic acid. After centrifugation, the clear supernatant extract (15 μL) was directly injected into the HILIC/MS/MS instrument, and each drug was separated on a Unison UK-Amino column (50 mm × 3 mm i.d., 3 μm particle size) with a linear gradient elution system composed of 10 mM ammonium acetate (pH 6.8) and acetonitrile at a flow rate of 0.7 mL/min. We performed quantification by multiple reaction monitoring (MRM) with negative-ion atmospheric-pressure chemical ionization. Results Distinct peaks were observed for the drugs on each MRM channel within 2 min. The regression equations showed good linearity within the range 0.04-4.0 μg/mL for the tear and plasma samples with detection limits at 0.02-0.04 μg/mL. Recoveries for target analytes (FT and 5-FU) for the tear and plasma samples were in the 94-128% and 94-104% ranges, respectively. The intra- and inter-day coefficients of variation for the two drugs were lower than 10.8%. The accuracies of quantitation were 97-115% for both samples. Conclusions We established a high-throughput, reproducible, and practical procedure for analyzing FT and 5-FU in human tear and plasma samples using HILIC/MS/MS analysis with an aminopropyl-bonded mixed-mode separation column. This method can be applied to the high-throughput routines used in clinical analyses.

A new high-throughput method was developed for analysis of valproate in human plasma samples by QuEChERS extraction and gas chromatography–tandem mass spectrometry (GC-MS/MS). Plasma samples (0.2 ml) spiked with valproate and secobarbital- d 5 (internal standard) were diluted with 1.3 ml of distilled water. Acetonitrile (1 ml) was added followed by 0.4 g MgSO 4 and 0.1 g NaOAC. After a centrifugation step (2000 g for 10 min), 1 ml of the supernatant was transferred to a dispersive-solid phase extraction (dSPE) tube containing 150 mg MgSO 4 and 50 mg C 18 . This mixture was vortexed and centrifuged at 3000 g for 5 min, and then the upper layer was evaporated to dryness under a stream of nitrogen. The residue was dissolved in 40 μl ethyl acetate, and a 1-μl aliquot was injected into the GC-MS/MS. The GC separation of the compounds was achieved on a fused-silica capillary column Rxi-5Sil MS (30 m × 0.25 mm i.d.; 0.25-µm film thickness) and detected by MS/MS operating in electron ionization ion source mode. The regression equations showed excellent linearity ( r > 0.9997) from 50 to 5000 ng/ml for plasma, with limit of detection of 10 ng/ml. The extraction efficiency of valproate for plasma ranged between 71.2%–103.5%. The coefficient of variation was

Impact damage of laminated B4C ceramic samples was investigated using four types of aluminum sheets — without holes and with 25 4-, 8-, and 25-mm-diameter holes — at joining ratios of 100, 94, 76, and 45%. Four 1-mm-thick B4C ceramics plates were laminated using three aluminum sheets of the same type and joined at 700°C in vacuum. In impact damage tests using spherical SUJ-2 projectile with a diameter of 4 mm with a velocity of approximately 300 ms−1, bulk B4C showed a large conical crack and significant fractures; the conical crack in the laminated samples was smaller than that of the bulk B4C. However, the conical cracks of the laminated B4C with the joining ratio 45 to 96% were of the same size, irrespective of the joining ratios. The total load and induced pressure area on the rear side of laminated samples were smaller than that observed for bulk B4C, and total load and induced pressure area were similar for laminated samples with high and low joining ratios. The maximum pressure on the rear face of laminated B4C samples was higher than that observed for bulk B4C and increased with decreasing joining ratio of laminate interlayer.

A simple and sensitive method was developed and validated here for the analysis of thirteen nonsteroidal anti-inflammatory drugs (NSAIDs) in human plasma samples by hydrophilic interaction liquid chromatography (HILIC)-tandem mass spectrometry (MS/MS). A small volume of plasma (20μL) spiked with compounds was diluted with 80μL of 10-mM ammonium acetate followed by a simple protein precipitation with 400μL of acetonitrile. After centrifugation, the clear supernatant extract was directly injected into the HILIC-MS/MS, without any solvent evaporation and reconstitution steps. The chromatographic separation of the NSAIDs was achieved on a Unison UK-Amino HILIC column (50mm×3mm i.d., particle size 3μm) with a linear gradient elution system composed of 10mM ammonium acetate (pH 6.8) and acetonitrile at a flow rate of 0.4mL/min. The mass spectra obtained by HILIC-MS showed base peak ions due to [M+H](+) for indomethacin, oxaprozin, ketoprofen, alminoprofen, zaltoprofen, tiaprofenic acid, pranoprofen, and ketoprofen-d3 and due to [M-H](-) for etodolac, ibuprofen, diclofenac, fenoprofen, loxoprofen, naproxen, and ibuprofen-d3. Recoveries of these thirteen NSAIDs in plasma were 34.8-113% and the lower limits of quantitation were 0.125-1.25μg/mL. The intra- and interday coefficient of variations for all drugs in plasma were less than 14.6%. The data obtained from actual plasma determinations of zaltoprofen, ibuprofen, and diclofenac are also presented.

A rapid and simple microanalysis method using TopTip C18 spin tips, which are new micropipette tip spin columns for solid-phase extraction, was developed and validated for quantitative determination of methamphetamine and amphetamine in human plasma. All the solid-phase extraction procedures, including conditioning, sample loading, washing, and elution, using the TopTip C18 spin tips, were performed by centrifugation. The analytes were extracted within 7–8 min from 0.1 mL of plasma. The methanol-rich eluate was injected directly into a hydrophilic interaction liquid chromatography/tandem mass spectrometer in positive electrospray ionization mode with selected reaction monitoring. The analytes were separated on an Imtakt Unison UK-silica column using a gradient with methanol and 10 mmol/L ammonium acetate buffer as mobile phase at a flow rate of 0.5 mL/min. The recoveries of methamphetamine and amphetamine spiked into plasma were 82–95% and the limit of quantification of methamphetamine and amphetamine wer...

A high-throughput method for analysis of ramelteon, agomelatine, and melatonin in human plasma by ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS–MS) is presented. The LC system, MS–MS system, and separation column used were Waters Acquity UPLC, Acquity TQD, and Poroshell 120 EC-C18, respectively. For extraction of the target compounds, solid-phase extraction was performed with Oasis HLB cartridges. All compounds were detected with retention times of

A high-throughput method was developed for determinations of eight barbiturates (barbital, allobarbital, phenobarbital, cyclobarbital, amobarbital, secobarbital, thiopental, and thiamylal) in human plasma by on-line column-switching ultra-fast liquid chromatography–tandem mass spectrometry (MS–MS). Plasma samples (100 μl) spiked with the eight barbiturates and 5-(4-methylphenyl)-5-phenylhydantoin (internal standard) were diluted with 300 μl of 13.3 mM ammonium acetate/acetonitrile (33:67, v/v). After centrifugation and filtration, the clear supernatant was injected directly onto the extraction column (Oasis HLB cartridge column). The following procedure was fully automated. The analytes retained on the extraction column were eluted by backflushing of the extraction column and introduced onto the analytical column (Phenomenex Onyx monolithic C18 column, 100 mm × 4.6 mm i.d.) by column switching. Quantification was performed by multiple reaction monitoring with negative-ion atmospheric pressure chemical ionization. Good peak separation and peak shapes of the eight drugs were achieved within an analysis time of 3 min, including the extraction time. All drugs spiked into plasma showed recoveries of 80–93 %. The regression equations for the eight drugs showed excellent linearities in the range of 10–5000 ng/ml of plasma, and the limits of detection ranged from 1.0 to 10 ng/ml. The lower and upper limits of quantitation were 10–50 ng/ml and 5000 ng/ml, respectively. Intraday and interday coefficients of variation for all the drugs were not >9.1 %. The accuracies of quantitation were 92.0–108 %. The method was successfully applied to determination of the level of amobarbital in human plasma after its oral administration to a volunteer.

Three tetracyclic antidepressants, mianserin, mirtazapine, and setiptiline, were extracted from human plasma samples using a new micropipette solid-phase extraction tip containing a monolithic silica gel packing material, the MonoTip C18. The plasma samples (0.1 ml), which contained mianserin, mirtazapine, and setiptiline, were mixed with 330 μl of distilled water and 50 μl of 0.5 M glycine–sodium hydroxide buffer solution (pH 8). After centrifugation, the supernatant was extracted onto the C18 phase of the tip (pipette tip volume, 200 μl) by 25 sequential aspirating/dispensing cycles. The three analytes retained in the C18 phase were eluted with methanol by 5 aspirating/dispensing cycles. The eluate was subjected to measurements by gas chromatography (GC) with nitrogen–phosphorus detection (NPD). The recoveries of the three antidepressants were 84.6–99.6% and the limits of detection for each drug were between 2.4 and 15 ng/ml of plasma. The maximum intraday and interday coefficients of variation for the drugs was below 10.6%. Regression equations for the three drugs showed excellent linearity in the range of 50–5000 ng/ml for mianserin and mirtazapine and 50–10 000 ng/ml for setiptiline. The antidepressants were stable for at least 12 h at 4°C, 4 weeks at −80°C, and through three freeze–thaw cycles in plasma. The validated method was successfully used to quantify the plasma concentrations of mirtazapine in a human subject after oral administration of the drug. Although we achieved analyte detection with GC-NPD, the present monolithic micropipette extraction method for tetracyclic antidepressants seems to be very useful for combining it with GC–mass spectrometry (MS) and/or liquid chromatography–tandem MS to secure high simplicity, purification, reproducibility, and sensitivity.

Ceramics will be used for power generating systems in the next generation. When they are used in this system, damage due to foreign object is inevitable. However, few systematic and comprehensive investigations have been reported on this subject. Various ceramics including fiber-reinforced mortars were investigated to understand their behavior when impacted by a spherical projectile. The volume of the cone cracks was large in ceramics which underwent transgranular fracture, while it was small in which underwent an intergranular one. Even though the energy consuming ability by the formation of surfaces was low up to 3.5% of the kinetic energy of a projectile, this ability increased with the ratio of the intergranular fracture to the transgranular one. Boron carbide showed a lower pressure as compared to the other ceramics. Fiber reinforcing increased the ballistic limits, but no clear advantage was suggested when absorbing the kinetic energy of a projectile far over its limits.

Solid-phase extraction (SPE) using micropipette tips is a useful technique to prepare samples prior to mass spectrometry. However, most commercial SPE tips have loading capacities that are insufficient for quantitative determination. In this paper, we describe a rapid method for quantitative microanalysis of five phenothiazine derivatives, chlorpromazine, levomepromazine, promazine, promethazine and trimeprazine, using a recently introduced C(18) monolithic silica SPE tip, the MonoTip C(18), for extraction from human plasma. The drugs could be extracted within 5 min from 0.1-mL plasma samples, eluted with methanol, and the eluate injected directly into a gas chromatograph prior to mass spectrometry analysis. Only 0.7 mL of solvent was required for each step of the extraction process. The recoveries of the five phenothiazines spiked into plasma were 91-95% and the limits of quantification for each drug were between 0.25 and 2.0 ng/0.1 mL. The maximum intra- and inter-day coefficient of variation was 11%. The validated method was successfully used to quantify the plasma concentration of levemepromazine in a human subject after oral administration of the drug. This new method is expected to have wide applications as a pretreatment for the rapid, quantitative determination of drug concentrations in plasma samples.

Six nonsteroidal anti-inflammatory drugs (NSAIDs) in human plasma samples were analyzed by liquid chromatography (LC)-electrospray ionizationtandem mass spectrometry (MS-MS) using a hydrophilic polymer column (MSpak GF-310 4B), which enabled direct injection of crude biological samples. Separation of the six NSAIDs, alminoprofen, flurbiprofen, ibuprofen, pranoprofen, tiaprofenic acid, and zaltoprofen, was carried out using gradient elution with 10 mM ammonium acetate/acetonitrile. The mass spectra obtained by LC-single stage MS showed base peak ions due to [M+H]+ for alminoprofen, zaltoprofen, tiaprofenic acid, and pranoprofen, and [M-H]- for ibuprofen and flurbiprofen. Product ions were produced from each [M+H]+ or [M-H]- ion in the tandem mode. Quantitation was performed by multiple reaction monitoring with switching from positive to negative ion mode and vice versa. All drugs spiked into plasma showed recoveries of 77.0%–88.2%. The regression equations for the six drugs showed excellent linearity in the range of 0.01–25 μg/ml of plasma, and limits of detection were in the range of 0.002–0.005 μg/ml. Limits of quantitation were 0.01–0.02 μg/ml. Intraday and interday coeffi cients of variation for all drugs in plasma were not greater than 8.1%. The accuracy of quantitating the six drugs was in the range of 94.5%–110%. Data obtained from actual determinations of the levels of alminoprofen, pranoprofen, and ibuprofen in human plasma after oral administration are also presented.

For forensic toxicological analysis of human specimens, extractive pretreatments are critical for successful analysis of target compounds. Nowadays, solidphase extraction (SPE) cartridges or columns packed with silica-type or polymer-type spherical particles are most widely used. In recent years, monolithic sorbent products, which have sponge-like structures, have been developed for SPE. The most significant advantage of the monolithic sorbent is that it allows very fast flow through the sorbent structure. Utilizing this property, pipette tips and spin columns packed with the monolithic sorbent have become commercially available. In this review, we present some details of SPE techniques using the monolithic pipette tips and spin columns, and discuss their advantages. The recent development of molecularly imprinted polymers (MIPs), which can selectively trap target compounds and act as an SPE sorbent, is also discussed with consideration of their advantages and disadvantages in SPE.

97.4% of theoretical density was obtained for boron carbide (B 4 C) ceramics by heating up to 2226 °C in an Ar atmosphere containing gaseous Al and Si species without external pressure. Impurities and secondary phases in the sintered B 4 C samples were examined by X-ray fluorescence and X-ray diffraction analyses respectively, which revealed that both Al and Si elements infiltrated into the green compacts and reacted with B 4 C to form SiC, Al 4 C 3 and Al 4 SiC 4 during the sintering. Triple junctions observed in the polished surfaces of the densified samples were filled by the secondary phases, indicating formation of liquid phase during heating. Dilatometric measurements at a constant heating rate in the Ar gas with the metallic gas species demonstrated that the shrinkage started at around 1700 °C, which was the liquid-phase formation temperature for the system reported in the previous studies. It was supposed that the liquid phase might be responsible for the densification.

Ceramics will be widely used for enhancing the efficiency of power generating systems, particularly gas turbines. However, ceramics used in these systems suffer damage owing to impact by foreign objects. In this study, various ceramic plates are impacted by a spherical projectile with an impact velocity of 320 m/s. The volume of the cone cracks formed on the plates decreases with an increase in the fracture toughness of the ceramic material. No cone cracks are formed on the zirconia (3Y-TZP) plate because crack formation is prevented by stress-induced phase transformation outside the impacted region. The volume of the cone crack is higher and the energy consumed by surface formation is smaller in transgranular-fractured ceramics than in intergranular-fractured ones. The fracture process can be controlled by controlling the characteristics of the grain boundaries, as well as by stress-induced phase transformation.

The Local Lymph Node Assay (LLNA) is now regarded as the worldwide standard. The analysis of accumulated LLNA data reveals that the animal strains and vehicles employed are likely to affect LLNA results. Here we show that an obvious strain difference in the local lymph node response was observed between DMSO-treated CBA/CaOlaHsd and CBA/CaHsdRcc mice. We also show that a vehicle difference in the response was observed when CBA/CaHsdRcc mice were exposed to 6 vehicles; 4:1 v/v acetone/olive oil (AOO), ethanol/water (70% EtOH), N,N-dimethylformamide (DMF), 2-butanone (BN), propylene glycol (PG), and dimethylsulfoxide (DMSO). The dpm/LN level was lowest in the 70% EtOH group and highest in the DMSO group. When alpha-hexylcinnamaldehyde (HCA) was used as a sensitizer for the LLNA, HCA was a weak sensitizer when AOO or DMSO was used as a vehicle, but a moderate sensitizer when the other 4 vehicles were used. This study showed that there are vehicle differences in the local lymph node response (dpm/LN level) in the LLNA and that the sensitization potency of HCA may be classified in different categories when using different vehicles. This suggests that careful consideration should be exercised in selecting a vehicle for the LLNA. A further comprehensive study will be needed to investigate why vehicle differences are observed in the LLNA.

Automated high-performance liquid chromatography/mass spectrometry (HPLC-MS) with backflush column-switching was established for ultra-fast determination of theophylline and caffeine. A 400-μl portion of serum sample diluted with ultrapure water was injected and transferred to an Oasis HLB cartridge used as a precolumn for extraction. After switching the valves, the analytes trapped in the precolumn were eluted in the backflush mode and separated with a Chromolith Performance RP-18e column (C18-bonded monolithic silica); the compounds in column effluents were then detected by atmospheric pressure chemical ionization (APCI)-MS. The present method successfully provided high-throughput determination of theophylline and caffeine within 2 min. Satisfactory linearity, reproducibility, and sensitivity could be obtained for analysis of therapeutic and toxic levels of both compounds. Because of the very simple procedure and high throughput using the conventional HPLC system, the present method seems to have high potential in the fields of forensic toxicology and emergency medicine.

A method for the simultaneous extraction of four tricyclic antidepressants from human plasma samples using pipette tip SPE with MonoTip C(18) tips is presented. Human plasma (0.1 mL) containing four tricyclic antidepressants (amitriptyline, amoxapine, imipramine, and trimipramine) and an internal standard (IS), protriptyline, was mixed with 0.4 mL of distilled water and 100 microL 1 M NaOH solution. After centrifugation of the mixture, the supernatant was extracted to the C(18) phase of the tip by 20 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained in the tip were eluted with methanol by five repeated aspirating/dispensing cycles. Without evaporation and reconstitution, the eluate was directly injected into a gas chromatograph injector and detected by a mass spectrometer with SIM in the positive-ion electron impact mode. Recovery of the four antidepressants and IS spiked into human plasma was 80.2-92.1%. The regression equations for the four antidepressants showed excellent linearity in the range of 0.2-40 ng/0.1 mL. LODs and LOQs for the four drugs were 0.05-0.2 ng/0.1 mL and 0.2-0.5 ng/0.1 mL, respectively. Intra- and interday CVs for the four drugs in plasma were no greater than 9.5%.

The psychoactive drugs methamphetamine and amphetamine are highly addictive. Because of this, their abuse is a significant problem, which can lead to fatality. Subsequently, in many instances, it is essential to determine if an individual has administered methamphetamine or amphetamine. Since the 1960s, the most common procedure to detect methamphetamine and amphetamine has been gas chromatography; however, new alternatives are being developed. In this chapter, methods for the screening, identification, and quantitation of methamphetamine and amphetamine in the blood are described. Examples of analytical methods from the literature, including operating conditions, are provided and their advantages and disadvantages discussed. Finally, new trends in analytical methods, such as the use of solid-phase extraction tips to enable miniaturization and molecularly imprinted solid-phase extraction to attain high analyte specificity, are presented. It is concluded that a combination of new techniques will be helpful for exploring molecular mechanisms of methamphetamine and amphetamine in the human body.

Three selective serotonin reuptake inhibitors (sertraline, fluvoxamine, and paroxetine) in human serum specimens were analyzed by liquid chromatography-tandem mass spectrometry using a new polymer column (Shim-pack MAYI-ODS), which enabled direct injection of crude biological samples without complicated pretreatments. Quantitation was made by mass chromatography for each product ion using dextromethorphan as internal standard. The recoveries of the three drugs from human serum were 29.2%–45.7% at 20 ng/ml and 52.0%–53.7% at 80 ng/ml. The regression equations showed good linearity for the three drugs in the range of 5–80 ng/ml. Each drug had a detection limit of 1–3 ng/ml. Thus, the present method of using a new polymer column is effective for rapid and sensitive analysis of both therapeutic and toxic levels of sertraline, fluvoxamine, and paroxetine in biological specimens.

Methamphetamine and amphetamine were extracted from human whole blood samples using pipette tip solid-phase extraction (SPE) with MonoTip C(18) tips, on which C(18)-bonded monolithic silica gel was fixed. Human whole blood (0.1 mL) containing methamphetamine and amphetamine, with N-methylbenzylamine as an internal standard, was mixed with 0.4 mL of distilled water and 50 microL of 5 M sodium hydroxide solution. After centrifugation, the supernatant was extracted to the C(18) phase of the tip (pipette tip volume, 200 microL) by 25 repeated aspirating/dispensing cycles using a manual micropipettor. Analytes retained in the C(18) phase were eluted with methanol by five repeated aspirating/dispensing cycles. After derivatization with trifluoroacetic anhydride, analytes were measured by gas chromatography - mass spectrometry with selected ion monitoring in the positive-ion electron impact mode. Recoveries of methamphetamine and amphetamine spiked into whole blood were more than 87.6 and 81.7%, respectively. Regression equations for methamphetamine and amphetamine showed excellent linearity in the range of 0.5-100 ng/0.1 mL. The limits of detection for methamphetamine and amphetamine were 0.15 and 0.11 ng/0.1 mL, respectively. Intra- and interday coefficients of variation for both stimulants were not greater than 9.6 and 13.8%, respectively. The determination of methamphetamine and amphetamine in autopsy whole blood samples is presented, and was shown to validate the present methodology.

An automated on-line method for simultaneous analysis of five phenothiazine drugs by high-performance liquid chromatography (HPLC)/sonic spray ionization mass spectrometry (SSI-MS) has been established, using backflush column switching. A 400-μl portion of serum sample diluted 81-fold with distilled water was subjected to the on-line system. In the system, an Oasis HLB cartridge was used as the precolumn for extraction; large molecules such as proteins in serum were discarded by use of distilled water containing 0.1% formic acid as a mobile phase. After switching a valve, the analytes trapped in the precolumn were eluted in the backflush mode and separated by a Chromolith Performance RP-18e column, which is composed of C18-bonded monolithic silica. The column effluents were then introduced into the SSI-MS. The present method provided successful separation and determination of six phenothiazines including an internal standard. Satisfactory linearities, reproducibility, and sensitivity were obtained at concentration levels that matched the toxic levels of phenothiazines. All drug peaks appeared within 18 min, and the system could be reequilibrated in only about 8 min for the next run. Because of the simplicity and rapidness of the method, it is likely to be useful in the fields of emergency medicine and forensic toxicology.

A method for the simultaneous determination of selegiline and its metabolite, desmethylselegiline, in human whole blood and urine is presented. The method, which combines a fiber-based headspace solid-phase microextraction (SPME) technique with gas chromatography-mass spectrometry (GC-MS), required optimization of various parameters (e.g., salt additives, extraction temperatures, extraction times and the extraction properties of the SPME fiber coatings). Pargyline was used as the internal standard. Extraction efficiencies for both selegiline and desmethylselegiline were 2.0-3.4% for whole blood, and 8.0-13.2% for urine. The regression equations for selegiline and desmethylselegiline extracted from whole blood were linear (r(2)=0.996 and 0.995) within the concentration ranges 0.1-10 and 0.2-20 ng/ml, respectively. For urine, the regression equations for selegiline and desmethylselegiline were linear (r(2)=0.999 and 0.998) within the concentration ranges 0.05-5.0 and 0.1-10 ng/ml, respectively. The limit of detection for selegiline and desmethylselegiline was 0.01-0.05 ng/ml for both samples. The lower and upper limits of quantification for each compound were 0.05-0.2 and 5-20 ng/ml, respectively. Intra- and inter-day coefficients of variation for selegiline and desmethylselegiline in both samples were not greater than 8.7 and 11.7%, respectively. The determination of selegiline and desmethylselegiline concentrations in Parkinson's disease patients undergoing continuous selegiline treatment is presented and is shown to validate the present methodology.

Mequitazine has been found to be extractable from human plasma samples using MonoTip C 18 tips, inside which C 18 -bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing mequitazine and cyproheptadine as an internal standard (IS) was mixed with 0.4 mL of distilled water and 25 μL of 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C 18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C 18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. Without evaporation and reconstitution, the eluate was injected into a gas chromatograph injector and detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of mequitazine and the IS from each other and from impurities was generally satisfactory using a DB-1MS capillary column (30 m × 0.32 mm i.d., film thickness 0.25 μm). The recoveries of mequitazine and the IS spiked into plasma were more than 90.0%. The regression equation for mequitazine showed excellent linearity in the range of 0.2–200 ng 0.1 mL −1 , and the detection limit was 0.05 ng 0.1 mL −1 of plasma. The intra-day and inter-day coefficients of variation for mequitazine in human plasma were not greater than 8.16 and 9.24%, respectively. Accuracy for the drug was in the range of 90.0–97.4%. The data obtained from determination of mequitazine in human plasma after oral administration of the drug are also presented.

A detailed procedure for analysis of four antiallergic drugs, ketotifen, olopatadine, cetirizine, and ibudilast, in human plasma by high-performance liquid chromatography (HPLC)-tandem mass spectrometry (MS-MS) using a new polymer column (MSpak GF), which enables direct injection of crude biological samples, is presented. The protein and/or macromolecule matrix compounds were first eluted from the column, while the drugs were retained on the polymer stationary phase. The analytes retained on the column were then eluted into an acetonitrile-rich mobile phase using a gradient separation technique. All compounds showed base peaks due to [M + H]+ ions by HPLC-MS with positive ion electrospray ionization, and the product ions were produced from each [M + H]+ ion by HPLC-MS-MS. Quantification was made by selected reaction monitoring. The recoveries of the four antiallergic drugs spiked into plasma were 51.7–95.5%. The regression equations for the four antiallergic drugs showed excellent linearity in the range of 1–100 ng/ml of plasma. The detection limit was 0.5 ng/ml for all compounds. The intraday and interday precisions for the drugs in plasma were not greater than 9.5%. The data obtained from actual determination of the antiallergic drugs in human plasma after their oral administration are also presented for validation of the method.

Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18-bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 µL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m × 0.32 mm i.d., film thickness 0.25 µm). The recoveries of the ten antihistamines spiked into plasma were 73.8–105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02–5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented. Copyright © 2006 John Wiley & Sons, Ltd.

Three muscle relaxants, tolperisone, eperisone, and tizanidine, were found to be extractable from human whole blood and urine samples by solid‐phase extraction (SPE) with a Sep‐Pak C18 cartridge. Their determination was made using capillary gas chromatography with nitrogen phosphorus detection. Recoveries of the three drugs were 80.0%–97.2% for whole blood and 82.0%–94.5% for urine. The coefficients of within‐day variation in terms of recovery for all compounds in whole blood and urine samples were 2.2%–9.1% and 6.9%–9.6%, respectively; those of day‐to‐day variation for the compounds in both samples were not greater than 18.1%. The regression equations for the compounds showed excellent linearity with detection limits of 1.6–7.7 ng mL−1 for whole blood and 6.0–8.0 ng mL−1 for urine. The data obtained for actual determination of tolperisone in a subject after ingestion of the drugs are also presented.

Simultaneous determination of seven barbiturates in human whole blood and urine by combining direct immersion solid-phase microextraction (DI-SPME) with gas chromatography-mass spectrometry (GC-MS) is presented. The main parameters affecting the DI-SPME process, such as SPME fibers, salt additives, pHs, extraction temperatures and immersion times were optimized for simultaneous determination of the drugs. The extraction efficiencies were 0.0180-0.988 and 0.0156-2.76% for whole blood and urine, respectively. The regression equations of the drugs showed excellent linearity for both samples; the correlation coefficients (r(2)) were 0.994-0.999. The detection limits for whole blood were 0.05-1 microg x ml(-1), and those for urine 0.01-0.6 microg x ml(-1). Actual quantitation could be made for pentobarbital in whole blood and urine obtained from volunteers, who had been orally administered a therapeutic dose of the drug. The DI-SPME/GC-MS procedure for barbiturates established in this study is simple and sensitive enough to be adopted in the fields of clinical and forensic toxicology.

A rapid determination method for pentazocine in human plasma without complicated pretreatments has been constructed by liquid chromatography/mass spectrometry (LC/MS) with sonic spray ionization (SSI) using an Oasis HLB cartridge column. The reliability on our method was investigated for human plasma samples spiked with pentazocine and dextromethorphan as internal standard. The regression equation for pentazocine showed good linearity in the ranges of 30–1,250 and 1,250–10,000 ng ml−1; the detection limit was 19.5 ng ml−1 in human plasma. The sensitivity, accuracy and precision were satisfactory to quantify the wide range of therapeutic to toxic levels. Our method established enabled the determination of a single sample of pentazocine in human plasma only within 4 min, and allowed analysis of more than 100 samples per day. The present method seems applicable for actual cases encountered in the forensic and clinical practices.

Three benzodiazepines, etizolam, brotizolam and lorazepam, have been analyzed from human plasma and urine samples by high-performance liquid chromatography–mass spectrometry (HPLC–MS) with a new polymer column (MSpak GF), which enabled direct injection of crude biological samples. The recoveries of the three benzodiazepines spiked into plasma and urine were 81.7–90.7 and 78.7–91.5%, respectively. The regression equations for the three benzodiazepines showed excellent linearity in the range 10–500 ng ml−1 of plasma or urine. The detection limits were 2 ng ml−1 for etizolam and brotizolam, 5 ng ml−1 for lorazepam in both samples. The intra- and inter-day precisions for plasma and urine were not greater than 12.7%. The data obtained from determination of the benzodiazepines in rat plasma after oral administration of the drugs are also presented.

We have presented a simple and sensitive method for determining pethidine, a narcotic analgesic drug in body fluids by gas chromatography–tandem mass spectrometry (GC–MS/MS). Pethidine and 4′-piperidinoacetophenone (internal standard) were extracted from body fluids with Bond Elut C 18 columns; the recoveries were above 85% for both compounds. The calibration curves for blood and urine showed good linearities in the range of 1.25–40 ng/ml. Its detection limits (signal-to-noise ratio=3) were estimated to be approximately 0.5 ng/ml of whole blood and urine.

Sonic spray ionization (SSI) was compared with atmospheric pressure chemical ionization (APCI) as an interface for liquid chromatography (LC)-mass spectrometry (MS) for the analysis of some local anesthetics. Peaks at [M+H]+ constituted the base peaks for all compounds by both SSI and APCI, except for prilocaine. The sensitivities by SSI for tetracaine, benzoxinate, dibucaine, bupivacaine and mepivacaine were 4–16 times higher than those by APCI; those by SSI for procaine and lidocaine were equivalent to those by APCI. Only for prilocaine was the sensitivity by SSI two times lower than that by APCI. In view of the higher sensitivities obtained for many local anesthetics by SSI, we established a detailed procedure for the assay of these drugs in human plasma and urine by LC-MS with SSI in combination with a diol-bonded silica gel HPLC column that enabled direct injection of crude biological samples without complicated pretreatment. The recoveries, sensitivities, accuracies and precisions were found satisfactory to quantitate them at their therapeutic levels.

A new method for determination of o-, m- and p-cresols and phenol in human body fluids by capillary gas chromatography (GC) has been developed using cryogenic oven trapping. After heating a whole blood or urine sample containing the four compounds and 2,4-dimethylphenol as internal standard in a 7.5 mL-vial at 100°C for 10 min, 5 mL of headspace vapor was drawn into a gastight syringe. All vapor was introduced through an injection port of a GC instrument in the splitless mode into an α-DEX 120 middle-bore capillary column at 0°C of oven temperature for trapping the compounds; the oven temperature was programmed up to 170°C for their detection by GC with flame ionization detection. The present conditions gave sharp peaks for the compounds, a good separation of each peak and low background impurities for whole blood and urine samples. The regression equations for all compounds showed good linearity in the range of 1–10 µg 0.5 mL−1, with r values of 0.9983–0.9998, for both samples. The detection lim...