Determination of medetomidine, atipamezole and midazolam in pig plasma by liquid chromatography-mass spectrometry

Medetomidine, atipamezole and midazolam in pig plasma were determined by liquid chromatography-mass spectrometry (LC-MS) with an atmospheric pressure chemical ionization interface system by the use of detomidine as an internal standard. The method was applied to studies of pharmacokinetic behaviour of these drugs.     

High-performance liquid chromatography-mass spectrometry for the quantification of nortriptyline and 10-hydroxynortriptyline in plasma

A highly sensitive and selective method for the quantification of nortriptyline and its major 10-hydroxy metabolite in plasma is described. The method is based on liquid-liquid extraction in combination with acid dehydration of the 10-hydroxy metabolite to the less polar 10,11-dehydronortriptyline. Deuterium labelled internal standards ([2H4]NT and [2H3]10-OH-NT) were used and the compounds were separated by reversed-phase HPLC and detected using atmospheric pressure chemical ionisation and mass spectrometry. The limit of quantification was 0.8 ng/ml for both compounds. A 1-ml volume of plasma was used for analysis in the concentration range 0.8-32 ng/ml. The within- and between-day coefficients of variation were 11% in the low, 1.6 ng/ml range, and 7% at 8 ng ml/ml. Using this method it was possible to quantify plasma concentrations for 168 h following a single oral dose of 25 mg of nortriptyline with good accuracy and precision.     

Characterization of cisplatin-glutathione adducts by liquid chromatography-mass spectrometry. Evidence for their formation in vitro but not in vivo after concomitant administration of cisplatin and glutathione to rats anc cancer patients

After incubation of equimolar amounts of cisplatin (CDDP) and glutathione (GSH) in phosphate buffer pH 7.4 at 37 degrees C, we detected two CDDP-GSH adducts whose structures, characterized by LC-MS, corresponded to cis-[Pt(NH3)2Cl(SG)] and cis-([Pt(NH3)2Cl]2(mu-SG))+. The latter is a new CDDP-GSH adduct, which was postulated but never structurally characterized so far. Rats and patients were given a 15-min intravenous infusion of CDDP (10 mg/kg to rats and 25 mg/m2 to patients) preceded by a GSH intravenous administration (200 mg/kg to rats as a bolus and 1.5 g/m2 to patients as a 15-min infusion). After the administrations, CDDP-GSH adducts were absent in rat and human plasma ultrafiltrates. The discrepancy between in vitro and in vivo findings can be explained based on pharmacokinetic considerations.     

Screening of chlorpropamide in horse plasma by high-performance liquid chromatography with ultraviolet absorbance detection, and confirmation by gas chromatography-mass spectrometry

A chromatographic method was developed to detect and confirm the presence of chlorpropamide (I) in horse plasma samples, for antidoping control. The plasma sample (1 ml) was extracted with dichloromethane and screened by high-performance liquid chromatography, and confirmation of the drug's presence was accomplished by using gas chromatography-mass spectrometry (GC-MS). The limit of detection was found to be 3.5 ng/ml at a signal-to-noise ratio of three. Derivatization of I with N,O-bis-(trimethylsilyl)trifluoroacetamide with 1% trimethylchlorosilane allowed for highly stable, accurate and sensitive GC-MS analysis. Plasma samples collected after the administration of diabinese were positive for I (one-five days) in all samples analysed.     

Effects of p,p'-DDE and some other chlorinated hydrocarbons on the formation of prostaglandins by the avian eggshell gland mucosa

Some structurally related chlorinated hydrocarbons were investigated for their effects on the production of prostaglandins by the eggshell gland mucosa of ducks and domestic fowl. Formation of PGF2 alpha, PGE2 and TxB2 by homogenates of domestic fowl eggshell gland mucosa was significantly inhibited by in vitro addition of p,p'-DDE, Arochlor 1242 and, to a lesser extent, Arochlor 1260, but not by p,p'-DDT and o,p'-DDE. Comparatively, in duck eggshell gland mucosa homogenates, synthesis of the same prostaglandins was somewhat more sensitive to inhibition by 5 microM p,p'-DDE added in vitro. Eggshell gland mucosa synthesized significantly more PGF2 alpha, PGE2 and TxB2 than did the mucosa of the magnum and isthmus regions of the oviduct. Duck eggshell gland mucosa homogenates synthesized significantly more prostaglandins than similar homogenates from the domestic fowl, and, considering the former synthesis of PGF2 alpha was significantly higher when ducks were slaughtered at 08:00 than at 16:00 hours. In ducks, dietary administration of 40 ppm, p,p'-DDE for 45 days resulted in 21% eggshell thinning compared to the contemporary control values. This treatment also resulted in notable effects in homogenates of the eggshell gland mucosa, as compared to controls: Ca2+ uptake was reduced by 43%, synthesis of PGF2 alpha, PGE2 and TxB2 was reduced by 26%, 38% and 53%, respectively; the Ca content was increased to 145%. The role of p,p'-DDE in inhibiting prostaglandin formation in the eggshell gland is discussed as a mechanism of the eggshell thinning action of this chlorinated hydrocarbon.     

Measurement of nitrite and nitrate in plasma, serum and urine of humans by high-performance liquid chromatography, the Griess assay, chemiluminescence and gas chromatography-mass spectrometry: interferences by biogenic amines and N(G)-nitro-L-arginine analogs

In this paper, the HPLC method for the measurement of nitrite and nitrate in serum of humans newly reported by E1 Menyawi et al. is discussed, especially in regard to the extremely low nitrate levels measured in serum of healthy humans. From the discussion, it is concluded that: (1) Biogenic amines at physiological concentrations do not significantly interfere with the batch Griess assay. (2) The HPLC method of E1 Menyawi et al. does not reveal accurate levels for serum nitrate. (3) In serum and plasma of healthy humans, nitrate ranges within 15-70 microM. (4) Exogenous NG-nitro-L-arginine analogs can interfere with the measurement of nitrate in human plasma and urine by the batch Griess assay, chemiluminescence and GC-MS; interferences can be effectively eliminated by solid-phase extraction on cation-exchangers.     

Studies on the metabolism and toxicological detection of the amphetamine-like anorectic mefenorex in human urine by gas chromatography-mass spectrometry and fluorescence polarization immunoassay

Studies on the metabolism and on the toxicological analysis of mefenorex [R,S-N-(3-chloropropyl)-alpha-methylphenethylamine, MF] using gas chromatography-mass spectrometry (GC-MS) and fluorescence polarization immunoassay (FPIA) are described. The metabolites were identified in urine samples of volunteers by GC-MS. Besides MF, thirteen metabolites including amphetamine (AM) could be identified and three partially overlapping metabolic pathways could be postulated. For GC-MS detection, the systematic toxicological analysis procedure including acid hydrolysis, extraction at pH 8-9 and acetylation was suitable (detection limits 50 ng/ml for MF and 100 ng/ml for AM). Excretion studies showed, that only AM but neither MF nor its specific metabolites were detectable between 32 and 68 h after ingestion of 80 mg of MF. Therefore, misinterpretation can occur. The Abbott TDx FPIA amphetamine/methamphetamine II gave positive results up to 68 h. All the positive immunoassay results could be confirmed by the described GC-MS procedure.     

Dentine hypersensitivity: the effects of brushing desensitizing toothpastes, their solid and liquid phases, and detergents on dentine and acrylic: studies in vitro

Dentine exhibiting symptoms of dentine hypersensitivity has tubules open at the dentine surface and patent to the pulp. The mechanisms whereby dentinal tubules are exposed is ill understood but probably involves a variety of abrasive and/or erosive agents. This study in vitro examined the quantitative and qualitative effects of toothpastes, their solid and liquid phases and detergents on dentine and acrylic. Abrasion of dentine and acrylic were measured by surfometry. Morphological changes to dentine were assessed by scanning electron microscopy. Abrasion of dentine and acrylic by toothpastes increased with increasing brushstrokes with marked differences in the extent of abrasion between different pastes. Brushing dentine with water or detergents produced progressive abrasion but which appeared to plateau around 2 microm loss. Water and detergents produced minimal effects on acrylic. At 5000 strokes dentine abrasion by solid phases was less than the parent toothpastes but the ranking order of abrasivity was the same as the parent toothpastes. Loss of dentine produced by liquid phases was minimal and in the order of 1-2 microm. Observationally, all toothpastes removed at least the dentine smear layer to expose many tubules; with one desensitizing product leaving a particulate deposit occluding most tubules. The solid phases of the toothpaste produced identical morphological changes to the parent paste. The liquid phases and detergents all exposed dentinal tubules by 5000 strokes. Water had little or no effect on the dentine smear layer. It is concluded that toothpastes, solid phase, liquid phase and detergents have the potential to abrade or erode dentine to a variable degree and result in tubule exposure. The effects of the liquid phases and detergents appear limited to the removal of the smear layer. Such detrimental effects seen in vitro could have relevance to the aetiology and management of dentine hypersensitivity. Toothpaste formulations which despite exposing tubules have ingredients capable of occluding tubules may be an area of development for such products.     

A model for the formation and solidification of grain boundary liquid in the heat-affected zone (HAZ) of welds

The rapid thermal cycle experienced in most welding operations can promote the constitutional liquation of precipitates in certain alloy systems. Grain boundary liquid films form in the subsolidus portion of the heat-affected zone (HAZ) as a consequence of constitutional liquation. Rapid cooling limits the extent of solute diffusion into the matrix from the grain boundary liquid and hence extends its solidification temperature range. Liquation cracking can occur in the HAZ if the grain boundary film exists at a time when the local thermal stresses become tensile. Hence, in order to predict the liquation cracking susceptibility of an alloy under a given welding condition, both the microstructural evolution which centers around grain boundary liquation and the stress generation have to be modeled. This article addresses the issue of microstructural evolution and attempts to present a model for the formation of grain boundary liquid during the heating cycle and its solidifiction during the cooling cycle. The variables which increase the life of the transient grain boundary liquid during the thermal cycle are identified. The onedimensional (1-D) model presented here is an important first step toward the ability to predict liquation cracking susceptibility of an alloy during welding.     

Structure-function studies on the inhibition of binding of alpha-thrombin to platelet GpIb alpha by the peptide D-Y-Y-P-E and the artifactual inhibitory activity of C-terminal E in this peptide

In papillary thyroid carcinoma lymphnode metastases at presentation do not seem to adversely affect survival, but do increase the risk of loco-regional tumor recurrence. The value of systematic versus selective lymphadenectomy is far less standardized, whereas the role of postoperative radioiodine in preventing either nodal recurrence or cancer death remains controversial. Clinical data of 36 N+ patients with papillary thyroid carcinoma who had undergone from 1990 to 1996 ipsilateral or bilateral neck dissection were retrospectively reviewed, to analyse the value of systematic lymphadenectomy. In our series of 50 extensive lymph node dissections (levels 2-6), the number of metastases in each specimen (mean value: 5) and the incidence of multiple level metastases (36%) were high. In 37.5% of the metastases at level 6 and in 11.1% at level 4, coexisting nodal involvement at level 2 was observed, without metastasization at intermediate levels. Multiple levels metastases and skip metastases were present in at least one third of the patients and could be excised only performing a complete dissection of the levels 2-6. Extra-capsular spread was found in 56% of the specimens. In 64.3% of these cases a functional neck dissection was performed. A modified radical or radical neck dissection was carried out in the other 35.7% of the cases. These patients received modified radical neck dissection (functional dissection with sacrifice of internal jugular vein) in 60% of the cases and radical neck dissection in the other 40%. In papillary thyroid carcinoma extensive lymphnode dissection at presentation has been stated to offer no advantage versus selective lymphadenectomy, causing increased morbidity. However, experienced surgeons report a low incidence (less than 5%) of accessory spinal nerve and cervical plexus permanent sequelae after functional neck dissection. In our opinion, patients with cervical lymph node metastases require a complete loco-regional neck dissection. Systematic lymphadenectomy, performed by lateral neck plus upper anterior mediastinal dissection, can yield a high disease-free survival. Moreover, this can limit the overall radio-iodine therapeutic dose and the risk of de-differentiation of recurrent tumor to the anaplastic type in patients with a long-term and near normal life-span.     

Improved detection of polycyclic aromatic compounds in complex mixtures by liquid chromatographic fractionation on poly(divinylbenzene) prior to gas chromatography-mass spectrometry. Application to the analysis of diesel particulates

The Japanese pufferfish Fugu rubripes has a 400 Mb genome with high gene density and minimal non-coding complexity, and is therefore an ideal vertebrate model for sequence comparison. The identification of regions of conserved synteny between Fugu and humans would greatly accelerate the mapping and ordering of genes. Fugu C9 was cloned and sequenced as a first step in an attempt to characterize the region in Fugu homologous to human chromosome 5p13. The 11 exons of the Fugu C9 gene share 33% identity with human C9 and span 2.9 kb of genomic DNA. By comparison, human C9 spans 90 kb, representing a 30-fold difference in size. We have also determined by cosmid sequence scanning that DOC-2, a tumour suppresser gene which also maps to human 5p13, lies 6-7 kb from C9 in a head-to-head or 5' to 5' orientation. These results demonstrate that the Fugu C9/DOC-2 locus is a region of conserved synteny. Sequence scanning of overlapping cosmids has identified two other genes, GAS-1 and FBP, both of which map to human chromosome 9q22, and lie adjacent to the Fugu C9/DOC-2 locus, indicating the boundary between two syntenic regions.     

Automated sample preparation for the determination of budesonide in plasma samples by liquid chromatography and tandem mass spectrometry

An automated bioanalytical method for the determination of the glucocorticosteroid drug budesonide in plasma samples at pM levels was investigated. The method was built using three separate automated analytical steps with manual transfer of samples between them. In the first step, a Tecan RSP150 (Genesis) pipetting robot was used to transfer 1 ml of centrifuged plasma samples and deuterated budesonide internal standard solutions into tubes and to homogenise the resulting admixture. In the second step, a solid-phase extraction was performed using an ASPEC Xli (Gilson) with 100 mg Isolute C18 columns. In order to avoid conventional time-consuming evaporation and reconstitution steps, the solid-phase extraction was coupled on-line to a trace enrichment system for further purification and concentration of the sample extracts. The concentrated samples were eluted in 300 microliters ethanol into injection vials, which were capped and transferred to the autosampler in the detection system. In the third step, the pre-treated samples were chromatographed in a gradient LC system and detected using a tandem MS system (Finnigan TSQ 7000), with an atmospheric pressure chemical ionisation interface. The described Analytical System consisting of one Tecan robot, two ASPEC systems and one LC-MS-MS system may analyse up to about 800 samples a week with less routine work for the analyst. The concentration range studied was 15 to 2500 pM in 1 ml spiked plasma samples and the limit of quantitation for the described method was determined as 15 pM, as defined by accuracy and precision better than 20%.     

Role of polymorphonuclear leucocytes and oxygen-derived free radicals in the formation of gastric lesions induced by HCl/ethanol, and a possible mechanism of protection by anti-ulcer polysaccharide

This study examined the role of oxygen-derived free radicals in the pathogenesis of gastric mucosal lesions induced by HCl/ethanol. Superoxide dismutase, and catalase, and their combination reduced gastric lesion formation in mice. Gastric lesions were also reduced in mice treated with cyclophosphamide or anti-neutrophils, but not in mice treated with allopurinol or desulphated-carrageenan. Cobra venom factor did not reduce lesion formation. These results suggested that oxygen-free radicals may contribute to the formation of gastric mucosal lesions induced by HCl/ethanol, and that oxygen radicals were generated from neutrophils but not from xanthine oxidase. Anti-ulcer pectic polysaccharide, bupleuran 2IIc, which was recently isolated from the roots of Bupleurum falcatum L., showed potent inhibition of HCl/ethanol-induced gastric lesions in mice. Bupleuran 2IIc seemed to scavenge hydroxyl radical effectively. It was suggested that this anti-ulcer polysaccharide may provide protection to the gastric mucosa by scavenging oxygen-free radicals.     

Thermodynamic laws of the oxygen solubility in liquid metals (Ni,Co, Fe,Mn, Cr) and the formation of oxygen-containing solutions in the alloys based on them

The solubility of oxygen in liquid Ni, Co, Fe, Mn, and Cr metals (Group IV in the periodic table) has been found for the first time. Linear dependences of the oxygen solubility on the standard Gibbs energy for the oxidation reaction of a liquid metal with gaseous oxygen are found. The revealed function of oxygen solubility is of scientific importance and allows one to develop a theory of oxygen solutions in liquid metals and liquid multicomponent metallic compositions and to calculate the energies of mixing of liquid metals with oxygen from ΔG _MO ^° for metal oxidation reactions with allowance for pseudoregular-solution model equations. Using the energies of mixing and metal compositions, we calculated the equilibrium oxygen concentrations in a metal molten pool at the end of oxidation stage of melting 08Kh18N10T steel in an arc furnace. This fact indicates practical importance of the found function of the oxygen solubility in metals.     

直读发射光谱法测定银硼钼锡铅的载体缓冲剂研究

研究推荐以Al_2O_3、K_2S_2O_7、SiO_2、BaCO_3、NaF、S、CaCO_3、Fe_2O_3为主要组分的载体缓冲剂,通过与地球化学样品中待测元素发生热化学反应生成氟化物、硫化物确保其蒸发浓集率,与样品基体生成难以挥发的硅铝酸盐降低其干扰程度。在此基础上建立了直读光谱快速测定Ag、B、Mo、Sn、Pb的单电极载体蒸馏法,采用国家一级标准物质校准工作曲线及分析结果的量值溯源,检出限分别为Ag 0.006μg/g、B 0.84μg/g、Mo 0.08μg/g、Sn 0.19μg/g、Pb 0.59μg/g,待测元素结果的精密度≤8.14%、准确度≤0.089,满足多目标地球化学调查、生态地球化学评价等要求。     

Studies on the determination of surface deuterium in AISI 1062, 4037, and 4140 steels by secondary ion mass spectrometry

The concentration of deuterium at the surface of cathodically charged high strength steels AISI 1062, 4037, and 4140 has been determined by secondary ion mass spectrometry (SIMS). The beneficial effects of pickling in NAP (a mixture of nitric, acetic, and phosphoric acids) to remove surfacebound deuterium have been observed. formerly with AMCA International Limited, Kanata, ON, Canada     

An automated method for the simultaneous determination of pravastatin and its main metabolite in human plasma by high-performance liquid chromatography/atmospheric pressure chemical ionization mass spectrometry

An unexpected t(1;19) translocation is described in a fetus. Inherited from the mother, this translocation was found during the course of a normal prenatal diagnosis made for maternal age. The very short length of chromosomal translocated segments and their labelling pattern made high-resolution cytogenetic methods and fluorescence in situ hybridization techniques necessary for the correct identification of this karyotype rearrangement, both in mother and fetus. Different modes of meiotic segregation, leading to potential erroneous prenatal diagnoses, are discussed.     

电感耦合等离子体原子发射光谱法测定钢中钨钼铌方法标准的探讨

采用盐酸、硝酸、氢氟酸分解试样,冒磷酸和高氯酸烟,如需要可加内标元素钇,加酒石酸溶液,采用电感耦合等离子体原子发射光谱法(ICP-AES)测定钢中钨、钼和铌。在优化仪器工作条件的基础上,综合考虑灵敏度和干扰情况选择最合适的分析线为W 207.911nm、Mo 202.030nm、Mo 281.615nm、Nb 309.418nm、Nb 316.340nm,并考察了可能的干扰元素。标准溶液系列与被测样品主体元素进行基体匹配,消除了基体效应的影响。各元素校准曲线线性相关系数均大于0.998,钨、钼、铌的检出限分别为0.0370、0.0379和0.0629mg/L。实验方法适用于钢中质量分数为0.005%~19.0%钨、0.005%~8.0%钼和0.005%~5.0%铌的测定,国内7家获得中国合格评定国家认可委员会认可的钢铁行业实验室之间的精密度试验证明方法具有良好的重复性和再现性。     

火花放电原子发射光谱法分析铜锌钎料中铜锌锰结果稳定性的探讨

铜锌钎料中Cu、Zn、Mn的化学成分测定长期采用化学湿法,但因为分析周期相对较长,很难满足现代生产企业对分析效率的要求。实验主要探讨了采用火花放电原子发射光谱法分析焊材铜锌钎料中Cu、Zn、Mn时,试样的制备、氩气输出压力、各项激发参数的设定等对Cu、Zn、Mn分析结果稳定性的影响。通过试验,确定镍基块状样品进行压样分析、采取酒精湿磨的样品表面处理方式;调节氩气输出压力为3.0MPa;选择光源分析参数中冲洗时间为4s、预燃时间为25s、积分时间为5s的改进措施。在优化的实验条件下,对1.5mm厚度铜锌钎料样品进行精密度考察,Cu、Zn、Mn测定结果的相对标准偏差(RSD,n=10)分别为0.14%、0.15%和0.98%;测定值与其他单位实验室提供的参考值一致。