Tetsuya Arinobu

Oceanic primary productivity and dissolved oxygen levels at the Cretaceous/Tertiary Boundary: Their decrease, subsequent warming, and recovery

Thirty-six different geochemical and foraminiferal analyses were conducted on samples collected at closely spaced intervals across the Cretaceous/Tertiary (K/T) boundary exposed at Caravaca, Spain. A rapid reduction in the gradient between δ13C values in fine fraction carbonate and benthic foraminiferal calcite and a decrease in the abundance of phosphorus (a proxy for organic carbon) and calcium were recorded in sediments 0–0.5 cm above the K/T boundary. These trends imply that an abrupt mass mortality occurred among pelagic organisms, leading to a significant reduction in the flux of organic carbon to the seafloor. In addition, variations in sulfur isotope ratios, the hydrocarbon-generating potential of kerogen (measured as the hydrogen index), and foraminiferal indices of dissolved oxygen level all imply that a rapid decrease in dissolved oxygen was coincident with the δ13C event. Evidence of the low oxygen event has also been recognized in Japan and New Zealand, suggesting that intermediate water oxygen minima were widely developed during earliest Danian time. A threefold increase in the kaolinite/illite ratio and a 1.2‰ decrease in δ18O (carbonate fine fraction) were recorded in the basal 0.1–2 cm of Danian age sediments. These trends suggest that atmospheric warming and an increase in surface water temperature occurred 0–3 kyr after the δ13C event. Recovery in the difference between δ13C values in the carbonate fine fraction and in benthic foraminiferal calcite as well as increases in phosphorus and calcium contents occur at the base of planktonic foraminiferal Zone Pla, implying that an increase in primary productivity commenced some 13 kyr after the K/T boundary. Tables A1-A3 are available on diskette or via Anonymous FTP from kosmos.agu.org directory APENO (Username = anonymous, Password = guest). Diskette may be ordered from American Geophysical Union, 2000 Florida Avenue, N.W., Washington, DC 20009 or by phone at 800-966-2481;

Liquid chromatographic–mass spectrometric determination of haloperidol and its metabolites in human plasma and urine

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Comparison of SSI with APCI as an interface of HPLC-mass spectrometry for analysis of a drug and its metabolites

Haloperidol and its two metabolites, reduced haloperidol and 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP) in human plasma and urine were analyzed by HPLC-MS using a new polymer column (MSpak GF-310), which enabled direct injection of crude biological samples without pretreatment. Recoveries of haloperidol and reduced haloperidol spiked into plasma were 64.4-76.1% and 46.8-50.2%, respectively; those for urine were 87.3-99.4% and 94.2-98.5%, respectively; those of CPHP for both samples were not less than 92.7%. The regression equations for haloperidol, reduced haloperidol and CPHP showed good linearity in the ranges of 10-800, 15-800 and 400-800 ng/ml, respectively, for both plasma and urine. Their detection limits were 5, 10 and 300 ng/ml, respectively, for both samples. Thus, the present method was sensitive enough for detection and determination of high therapeutic and toxic levels for haloperidol and its metabolites present in biological samples.

High-throughput determination of theophylline and caffeine in human serum by conventional liquid chromatography-mass spectrometry

Sonic spray ionization (SSI) was compared with atmospheric pressure chemical ionization (APCI) as an interface of high-performance liquid chromatography (HPLC)-mass spectrometry (MS) for sensitive analyses of a neuroleptic drug, haloperidol and its two metabolites, such as reduced haloperidol and 4-(4-chlorophenyl)-4-hydroxypiperidine (CPHP), in biological samples. For both SSI and APCI interfaces, HPLC-MS-MS gave higher sensitivity than HPLC-MS. The sensitivities by HPLC-SSI-MS-MS for haloperidol and reduced haloperidol were 100 and 30 times higher, respectively, than those by HPLC-APCI-MS-MS; no spectrum with recognizable peaks was obtained for CPHP with the APCI interface. Therefore, detection limits and regression equations were examined by the HPLC-SSI-MS-MS for human plasma and urine samples spiked with the above drug and its metabolites. Haloperidol, reduced haloperidol, and CPHP showed good linearity in the ranges of 5–800, 10–800, and 100–800 ng/mL, respectively, for both human plasma and urine; their detection limits were 2.5, 5, and 75 ng/mL, respectively, using a new polymer HPLC column which enabled direct application of biological samples.

Simple analysis of α-amanitin and β-amanitin in human plasma by liquid chromatography-mass spectrometry

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.

Comparison of sonic spray lonization with atmospheric pressure chemical lonization as an interface of liquid chromatography-mass spectrometry for the analysis of some local anesthetics

A number of reports are available in the literature that describe liquid chromatography-mass spectrometry (LC-MS) and LC-tandem mass spectrometry (LC-MS-MS) analysis of amanitins, very toxic mushroom toxins, in biological samples. However, the extractive pretreatment methods and LC separation column materials vary remarkably according to the different reports. This communication presents a very simple and suffi ciently sensitive method for LC-MS analysis of amanitins. A plasma sample was diluted with distilled water and buffer solution, and applied to a Discovery DSC 18 column (500 mg packing material), followed by washing with distilled water and elution with methanol. The extract, after evaporation and reconstitution in mobile phase solution, was subjected to LC-MS analysis with a conventional octadecyl LC separation column. The selected ion monitoring of α-amanitin and β-amanitin at m/z 919–921 and m/z 920–922, respectively, gave symmetrical peaks and good separation of both amanitin peaks. Using an external calibration method, linearity, detection limits, recovery rates, and precision were tested; they were all satisfactory. To our knowledge, the present method gives the simplest LC-MS analysis for amanitins among those so far reported. We recommend the method for use in actual forensic and clinical toxicological analysis of amanitins in biological samples.

Rapid analysis of sertraline, fluvoxamine, and paroxetine in serum specimens by LC-MS-MS using a new polymer column

SummarySonic 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.

Determination of nonsteroidal anti-inflammatory drugs in human plasma by LC-MS-MS with a hydrophilic polymer column

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.

An automated on-line method for simultaneous analysis of phenothiazines in human serum by high-performance liquid chromatography/sonic spray ionization mass spectrometry using backflush column switching

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.

A negative carbon isotope anomaly associated with the earliest Lopingian (Late Permian) mass extinction

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.