High QC Research Articles

A practical approach for the validation and clinical implementation of a high-sensitivity cardiac troponin I assay across a North American city

ObjectivesDespite several publications on the analytical performance of high-sensitivity cardiac troponin (hs-cTn) assays, there has been little information on how laboratories should validate and implement these assays into clinical service. Our study provides a practical approach for the validation and implementation of a hs-cTn assay across a large North American City. Design and methodsValidation for the Abbott ARCHITECT hs-cTnI assay (across 5 analyzers) consisted of verification of limit of blank (LoB), precision (i.e., coefficient of variation; CV) testing at the reported limit of detection (LoD) and within and outside the 99th percentile, linearity testing, cTnI versus hs-cTnI patient comparison within and between analyzers (Passing and Bablok and non-parametric analyses). Education, clinical communications, and memorandums were issued in advance to inform all staff across the city as well as a selected reminder the day before live-date to important users. All hospitals switched to the hs-cTnI assay concurrently (the contemporary cTnI assay removed) with laboratory staff instructed to repeat samples previously measured with the contemporary cTnI assay with the hs-cTnI assay only by physician request. ResultsAcross the 5 analyzers and 6 reagent packs the overall LoB was 0.6ng/L (n=60) with a CV of 33% at an overall mean of 1.2ng/L (n=60; reported LoD=1.0ng/L), with linearity demonstrated from 45,005ng/L to 1.1ng/L. Precision testing with a normal patient-pool QC material (mean range across 5 analyzers was 3.9–4.4ng/L) yielded a range of CVs from 7% to 10% (within-run) and CVs from 7% to 18% (between-run) with the high patient-pool QC material (mean range across 5 analyzers was 29.6–36.3ng/L) yielding a range of CVs from 2% to 5% (within-run) and CVs from 4% to 8% (between-run). There was agreement between hs-cTnI versus cTnI with the patient samples (slope ranges: 0.89–1.03; intercept ranges: 1.9–3.8ng/L), however, the median CV on patient samples <100ng/L across the analyzers was 5.6% for hs-cTnI versus 18.7% for the contemporary assay (p<0.001). Following the switch to hs-cTnI testing, no requests for repeat measurements were received. ConclusionsValidation and implementation of hs-cTnI testing across multiple sites requires collaboration within the laboratories and between hospital laboratories and clinical staff.

A Comparative Evaluation of Polystyrene Divinylbenzene Copolymer HPLC Columns on the Chromatographic Performance of the Compendial Method for Doxycycline Hyclate Capsules: Implications for Method Implementation of a Medical Countermeasure Medication

The purpose of this study was to evaluate the impact of polystyrene divinylbenzene copolymer HPLC columns on the chromatographic performance of the USP compendial method for doxycycline hyclate. The compendial method was implemented based on the assessment of the chromatographic performance of six USP defined L21 polystyrene divinylbenzene HPLC columns. Modifications to the method were based on USP for chromatography. The method was validated for the determination of doxycycline hyclate and its impurities in commercially available drug products. A number of different polystyrene-divinylbenzene columns were tested and failed to provide selectivity for the resolution of doxycycline and its impurities. Separation was optimally achieved on an Agilent PLPR-S column (250 × 4.6 mm, 8 μm) by using an Agilent 1260 series HPLC system. Doxycycline hyclate and its impurities were eluted isocratically at a flow rate of 1 mL/min with mobile phase and detected at 270 nm. The column temperature was maintained at 60oC. The method was validated according to USP category I requirements for Assay. Validation acceptance criteria were met in all cases. The analytical range for doxycycline hyclate was 50 - 250 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific. Both accuracy (95.1% - 102.4%) and precision (0.50% - 4.8%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing marketed products of doxycycline hyclate, in which results showed potency meeting USP acceptance criteria. In conclusion, this study described the remarkable differences in selectivity that were encountered during the implementation phase for the compendial methods for doxycycline and its impurities in marketed products and it could be used in the future to assss the product quality of doxycycline hyclate capsules stored in the National stockpiles.

Simultaneous quantification of lenalidomide, ibrutinib and its active metabolite PCI-45227 in rat plasma by LC–MS/MS: Application to a pharmacokinetic study

Efficacy assessments using a combination of ibrutinib and lenalidomide necessitate the development of an analytical method for determination of both drugs in plasma with precision. A high performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of lenalidomide, ibrutinib, and its active metabolite PCI45227 in rat plasma. Extraction of lenalidomide, ibrutinib, PCI45227 and tolbutamide (internal standard; IS) from 50μl rat plasma was carried out by liquid–liquid extraction with ethyl acetate:dichloromethane (90:10) ratio. Chromatographic separation of analytes was performed on YMC pack ODS AM (150mm×4.6mm, 5μm) column under gradient conditions with acetonitrile:0.1% formic acid buffer as the mobile phases at a flow rate of 1ml/min. Precursor ion and product ion transition for analytes and IS were monitored on a triple quadrupole mass spectrometer, operated in the selective reaction monitoring with positive ionization mode. Method was validated over a concentration range of 0.72–183.20ng/ml for ibrutinib, 0.76–194.33ng/ml for PCI-45227 and 1.87–479.16ng/ml for lenalidomide. Mean extraction recovery for ibrutinib, PCI-45227, lenalidomide and IS of 75.2%, 84.5%, 97.3% and 92.3% were consistent across low, medium, and high QC levels. Precision and accuracy at low, medium and high quality control levels were less than 15% across analytes. Bench top, wet, freeze–thaw and long term stability was evaluated for all the analytes. The analytical method was applied to support a pharmacokinetic study of simultaneous estimation of lenalidomide, ibrutinib, and its active metabolite PCI-45227 in Wistar rat. Assay reproducibility was demonstrated by re-analysis of 18 incurred samples.

O33: Quantification of morphine, 6-monoacetylmorphine, cyamemazine, meprobamate and caffeine in 11 fluids and tissues, using automated solid-phase extraction and gas chromatography – tandem mass spectrometry

Introduction The present study reports a validated automated solid-phase extraction (SPE) protocol associated to GC-MS/MS assay to quantify 5 drugs (caffeine, cyamemazine, meprobamate, morphine and 6-monoacetylmorphine (6-MAM)) in 11 biological matrices. Assessment of the protocol to be used as a starter set for the development of further analytical assays is demonstrated. Methods Analyses are performed on 200±5 mg of tissue samples for lung, kidney, liver, muscle and bone marrow, 500±10 mg for adipose tissue and brain, and 200μl for biological fluids (bile, blood, urine and vitreous humor). Automated SPE was performed using a Gx-271 ASPEC (Gilson Inc.) on Strata™ X-C (Phenomenex) SPE columns. The molecules were eluted in 2 different eluates, each analyzed by GCMS/ MS. A full validation was performed on BM, the most complex matrix, and partial validation on the other 10 matrices according to the validation protocol proposed by Cartiser et al. (J. Chrom. B, 2011). The sample preparation was assessed in blood, BM and lung for the analysis of 12 further compounds exhibiting varied physicochemical properties: (alimemazine, alprazolam, amitryptiline, citalopram, cocaine, diazepam, levomepromazine, nordazepam, tramadol, venlafaxine, pentobarbital, and phenobarbital). Results Extraction recovery range between 5.3% for morphine in brain to 78.4% for caffeine in bile. The limits of quantification were 12.5 ng/ml(ng/g) for 6-MAM, morphine and cyamemazine, 100 ng/ml (ng/g) for meprobamate and 50 ng/ml(ng/g) for caffeine. Precision and accuracy at the LOQ were respectively less than 20% and between 80% and 120% except for morphine in muscle (121.2%), meprobamate in kidney (138.6%), and cyamemazine in kidney (148.6%). None of the analytes demonstrated precision greater than 15% or accuracy outside of the 85–115% range in BM. Validation on the other matrices showed accuracy of 80–120% for all analytes, except for cyamemazine in kidney where accuracy was 135% at the high QC level. Precision was Conclusion An automated SPE protocol associated to GC-MS/MS analysis was developed for quantification of caffeine, cyamemazine, meprobamate, morphine and 6-MAM in 11 biological matrices. The performance of this assay allows application in forensic toxicology or pharmacokinetic studies. The extraction protocol can be used for targeted analysis of various basic drugs and, with optimization, for other drugs or screening procedures in complex matrices. It could thus be an interesting starting set for further development for laboratories seeking to optimize their activity and confronted to analysis of new compounds or new matrices.

Simultaneous quantification of ruxolitinib and nilotinib in rat plasma by LC–MS/MS: Application to a pharmacokinetic study

Efficacy assessments using a combination of ruxolitinib and nilotinib necessitate the development of a high precision analytical method for determination of both drugs in plasma. A high performance liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for the simultaneous determination of ruxolitinib and nilotinib in rat plasma. Extraction of ruxolitinib, nilotinib and dasatinib (internal standard; IS) from 50μl rat plasma was carried out by protein precipitation with methanol. Chromatographic separation of analytes was performed on YMC pack ODS AM (150mm×4.6mm, 5μm) column under gradient conditions with acetonitrile:2.0mM ammonium acetate buffer as the mobile phase at a flow rate of 1ml/min. Precursor ion and product ion transition for both analytes and IS were monitored on a triple quadrupole mass spectrometer, operated in the selective reaction monitoring with positive ionization mode. Method was validated over a concentration range of 0.16–247ng/ml for ruxolitinib and 0.86–219ng/ml for nilotinib. Mean extraction recovery for ruxolitinib, nilotinib, and IS of 99.6%, 97.6% and 90.3% were consistent across low, medium, and high QC levels. Precision and accuracy at low, medium and high quality control levels were less than 15% across analytes. Bench top, wet, freeze-thaw and long term stability were evaluated for both analytes. The analytical method was applied to support a pharmacokinetic study of simultaneous estimation of ruxolitinib and nilotinib in Wistar rat. Assay reproducibility was demonstrated by re-analysis of 18 incurred samples.

Development and validation of a sensitive LC–MS/MS method for the determination of d-serine in human plasma

A validated LC–MS/MS method was developed for the determination of d -Serine in human plasma. The method was fully validated for use with human plasma samples and was linear from 0.19 nmol/ml to 25 nmol/ml. The coefficient of variation was ≤5% for the high QC standards and ≤8% for the low QC standards in plasma. d -Serine and l -serine were resolved by pre-column derivatization using (R)-1-Boc-2-piperidine carbonyl chloride as the derivatizating agent. The method was used to determine the concentration of d-serine in plasma samples obtained in patients receiving a continuous 5-day intravenous infusion of (R,S)-ketamine. The changes in d-Ser levels varied in the six patients, with circulating d-Ser levels increasing as much as 35% in a patient, while decreasing 20% in a patient. While only preliminary data, the results suggests the potential importance in determining the d-Ser levels in plasma and their potential role in physiological response.

Sunitinib LC–MS/MS Assay in Mouse Plasma and Brain Tissue: Application in CNS Distribution Studies

Sunitinib malate is a multi-targeted tyrosine-kinase inhibitor, currently in clinical trials for glioma. Previously developed methods for preclinical studies in species such as mice have either employed high-performance liquid chromatography (HPLC) or did not describe a detailed analytical method, which could be employed by other preclinical laboratories. In this paper, we have developed and validated a simple, sensitive high-performance liquid chromatography tandem mass-spectrometric method (LC-MS/MS) for the determination of sunitinib concentration in mouse plasma and brain tissue homogenate using dasatinib-free base as the internal standard. A single step liquid-liquid extraction method was used for both the matrices. Since sunitinib exhibits light-induced E/Z isomerism, all sample preparation was done in light-protected conditions. Separation was performed on a ZORBAX Eclipse XDB C18 column 4.6 × 50 mm, 1.8 μm. The mobile phase consisted of 20 mM ammonium formate (with 0.1 % formic acid): acetonitrile (70:30, v/v) pumped isocratically at a flow rate of 0.25 mL min-1 with a total run-time of 13 min. The retention times of sunitinib and dasatinib were 7.8 and 5.5 min, respectively. The calibration curve was linear over the range from 1.95 to 500 ng mL-1 in both plasma and brain tissue homogenate with 1.95 ng mL-1 as the lower limit of quantification (LLOQ) for both the matrices. Inter- and intra-day accuracy and precision was <15 % for low QC, med QC and high QC and <20 % for LLOQ. The method was applied to a pharmacokinetic study in FVB wild-type mice to determine the plasma and brain concentrations after a single oral sunitinib malate dose of 20 mg kg-1.

Development and validation of a sensitive LC-MS/MS method for the determination of fenoterol in human plasma and urine samples.

Due to the lack of sensitivity in current methods for the determination of fenoterol (Fen), a rapid LC-MS/MS method was developed for the determination of (R,R')-Fen and (R,R';S,S')-Fen in plasma and urine. The method was fully validated and was linear from 50pg/ml to 2000pg/ml for plasma and from 2.500ng/ml to 160ng/ml for urine with a lower limit of quantitation of 52.8pg/ml in plasma. The coefficient of variation was <15% for the high QC standards and <10% for the low QC standards in plasma and was <15% for the high and low QC standards in urine. The relative concentrations of (R,R')-Fen and (S,S')-Fen were determined using a chirobiotic T chiral stationary phase. The method was used to determine the concentration of (R,R')-Fen in plasma and urine samples obtained in an oral cross-over study of (R,R')-Fen and (R,R';S,S')-Fen formulations. The results demonstrated a potential pre-systemic enantioselective interaction in which the (S,S')-Fen reduces the sulfation of the active (R,R')-Fen. The data suggest that a non-racemic mixture of the Fen enantiomers may provide better bioavailability of the active (R,R')-Fen for use in the treatment of cardiovascular disease.

Multicomponent high-performance liquid chromatography/tandem mass spectrometry analysis of ten chemotherapeutic drugs in wipe samples

Progress in chemotherapy leads to increased numbers and variety of chemotherapeutic drugs, and multicomponent analysis of these drugs is a necessary step. We used liquid chromatography-tandem mass spectrometry and developed a multicomponent analysis of ten drugs used in chemotherapy: vindesine, vincristine, vinblastine, doxorubicin, epirubicin, ifosfamide, cyclophosphamide, irinotecan, docetaxel, and paclitaxel. We selected five internal standards for each category of drug, because the ionization efficiencies of product ions varied widely. The total run time was 22min, applying a gradient elution of water and acetonitrile in the presence of 0.1% formic acid. The lower limit of quantification was 50ng/wipe samples for vindesine, vincristine, and vinblastine, and 5ng/wipe samples for the remaining seven drugs. Accuracy (88.6-112.9%, 85.2-111.7%) and precision (1.0-11.5%CV, 3.6-14.4%CV) in within-run and between-run assays of QC solutions were acceptable. Without outliers, in within-run and between-run assays of QC samples, accuracy was 90.6-113.9% and 91.1-130.4%, respectively, and precision was 2.2-19.0%CV and 4.8-14.9%CV, respectively. Accuracy and precision of High QC samples of irinotecan were deviated. Our analysis procedure has sufficient sensitivity and is convenient enough for regular monitoring.

Development and Application of a Validated HPLC Method for the Determination of Clindamycin Palmitate Hydrochloride in Marketed Drug Products: An Optimization of the Current USP Methodology for Assay

A simple efficient isocratic reversed-phase HPLC method was developed and validated for the determination of clindamycin palmitate hydrochloride (CPH) and its commercially available oral solution products. Separation was achieved on a Phenomenex Zorbax (Luna) cyano column (150 × 4.6 mm, 5 μm) with a Phenomenex cyano guard cartridge (4 × 3.0 mm) on Agilent 1050 series HPLC system. CPH and its resolution standard lincomycin were eluted isocratically at a flow rate of 1 mL/min with a simplified mobile phase (potassium phosphate buffer (5 mM, pH 3.0)—acetonitrile—tetrahydrofuran (20:75:5, v/v/v)) and detected at 210 nm. The column was maintained at 25?C. The method was validated according to USP category I requirements. Robustness and forced degradation studies were also conducted. CPH marketed drug products were obtained from a drug distributor and assayed for potency using the validated method. Validation acceptance criteria were met in all cases. The analytical range for CPH was 15 - 500 μg/mL and the linearity was r2 > 0.999 over three days. The method was determined to be specific and robust. Both accuracy (92.0% - 103.8%) and precision (0.67% - 1.52%) were established across the analytical range for low, intermediate and high QC concentrations. Method applicability was demonstrated by analyzing two marketed products of CPH, in which results showed potency >98%. The method was determined to be an enhancement over the current USP methodology for assay as a result of increased efficiency, reduced organic solvents and the elimination of matrix modifiers. This method was successfully applied for the quality assessment of: 1) currently marketed drug products and 2) will in future assess the product quality of novel dosage forms of CPH for pediatric use.

Modified master curve of ultra high strength steel

The classical Master Curve approach covers the ferritic steels with a yield strength range of 275 MPa–825 MPa. The ultra high strength steel S960 QC is out of this range, and it does not follow the formula determined in the ASTM E1921-05 Standard. In this paper, the results of the research program are presented, and a new Master-like curve is derived. The new curve preserves the basic features of the classical Master Curve; it simply widens the family of Master Curves.

Design and Optimization of Integrated MOS Varactors for High-tunability RF Circuits

This paper presents a highly tunable low-resistance (high QC), low-cost Metal Oxide Semiconductor (MOS) varactor realized in the 0.18 μm Complementary Metal Oxide Semiconductor (CMOS) technology for Wireless Local Area Network (LAN) high-frequency application. The varactor implemented in an accumulation-MOS mode of configuration exhibits a superior tuning percentage of 41% (0.98 pF ~ 0.40 pF). Various MOS varactor configurations are demonstrated comparatively.

Quantitative analysis of NIM811, a cyclophilin inhibitor, in human dried blood spots using liquid chromatography–tandem mass spectrometry

A high-performance liquid chromatography–tandem mass spectrometric (LC–MS/MS) method has been developed and validated for the quantitative analysis of NIM811, a cyclophilin inhibitor, in human dried blood spot (DBS) samples, which were produced by spotting 20 μl whole blood onto FTA cards. A 3 mm disc was cut from the DBS samples and extracted using methanol, followed by liquid–liquid extraction with MTBE. The reconstituted extracts were chromatographed using a Halo C 18 column and gradient elution for MS/MS detection. The possible impact of hematocrit, blood sample volume and punching location on DBS sampling was investigated. The results showed that blood sample volume or punching location has no impact on assay performance, but the presence of a high hematocrit resulted in significantly increased analyte concentrations measured from the high QC samples. The current method was fully validated over the range of 10.0–5000 ng/ml with correlation coefficients ( r 2) for three validation batches equal to or better than 0.991. The accuracy and precision (CV) at the LLOQ were −0.7 to 6.0% bias of the nominal value (10.0 ng/ml) and 10.2–2.3%, respectively. For the balance of QC samples (20.0, 50.0, 750, 1500 and 3750 ng/ml), the precision (CV) ranged from 3.2 to 11.7% and from 5.6 to 10.2%, respectively, for the intra-day and inter-day evaluations. The accuracy ranged from −6.8 to 8.5% and −0.2% to 2.7% bias, respectively, for the intra-day and inter-day batches. NIM811 is stable in the DBS samples for at least 24 h at room temperature and 4 h at 60 °C. Interestingly, the long term stability (LTS) assessment showed that the stability of the analyte is better when the DBS samples were stored at a lower storage temperature (e.g. ≤−60 °C) compared to storage at room temperature. This is probably due to the interaction of the additives and/or other materials (e.g. cellulose, etc) on the DBS card with NIM811, a cyclic peptide. The current methodology has been applied to determine the NIM811 levels in DBS samples prepared from a clinical study.

Direct quantitation of glucoraphanin in dog and rat plasma by LC–MS/MS

A rapid method to quantify levels of the β-thioglycoside N-hydroxyl sulfate, glucoraphanin, in dog and rat plasma to support pre-clinical toxicological and pharmacological studies has been developed using liquid chromatography–tandem mass spectrometry (LC–MS/MS). Glucoraphanin was extracted from plasma by protein precipitation with acetonitrile and separated via hydrophilic interaction liquid chromatography (HILIC) using a Luna 5 μm Silica (2) 100 Å column (50 mm× 2.0 mm) at a flow rate of 0.3 mL/min. Solvent A consisted of 200 mM ammonium acetate and formic acid (99:1, v/v) and Solvent B was acetonitrile. Initial conditions (90% Solvent B) were held for 0.01 min after injection, decreased to 40% in 0.5 min and held constant for 2.5 min, returning to initial conditions for 3 min (reequilibration time). Glucoraphanin was detected by MS/MS using a turbo ion spray interface as the ion source operating in negative ion mode. Acquisition was performed in multiple reaction monitoring mode at m/ z 435.8 → 96.7. The method was validated for the calibration range 10–2000 ng/mL. Within- and between-run precision for the low, mid and high QC levels was 8% R.S.D. or less and accuracy ranged from 100 to 113%. The lower limit of quantification was 10 ng/mL; calibration curves encompassed the range of plasma concentrations expected to be found in bioavailability and pharmacokinetics studies with glucoraphanin. The method has successfully been applied to the determination of glucoraphanin in dog and rat plasma and should be extendable to other species as well.

Enhancement of nonlinear optical properties of Au–TiO2 granular composite with high percolation threshold

AbstractTwo series of Au–TiO2 composite films with Au percola‐ tion threshold qC of 0.34 and 0.82 were prepared by using sputtering technique at the pressure of 5.0 × 10–2 and 8.0 × 10–2 Torr, respectively. As qC increases from 0.34 to 0.82, the plasmon resonant absorption of the composite films near qC shifts from about 700 nm to 760 nm, and the maximal second harmonic generation (SHG) intensity increases by 20%, the maximal nonlinear absorption coefficient increases from –3.0 × 104 cm/GW to 1.7 × 105 cm/GW, and the maximal nonlinear refraction index increases from a very small value to –2.6 cm2/GW. The large second‐ and third‐order optical nonlinearity of the Au–TiO2 composite films with high qC is attributed to the high density of Au particle in the nonconductive film and the strong local field enhancement caused by the surface plasmon resonant absorption. (© 2008 WILEY‐VCH Verlag GmbH &amp; Co. KGaA, Weinheim)

Trace level determination of trichloroethylene from liver, lung and kidney tissues by gas chromatography–magnetic sector mass spectrometry

Trichloroethylene (TCE) is a common industrial chemical that has been heavily used as a metal degreaser and a solvent for the past 100 years. As a result of the extensive use and production of this compound, it has become prevalent in the environment, appearing at over 50% of the hazardous waste sites on the US EPA’s National Priorities List (NPL). TCE exposure has been linked to neurological dysfunction as well as to several types of cancer in animals. This paper describes the development and validation of a gas chromatography–mass spectrometry (GC–MS) method for the quantitation of trace levels of TCE in its target tissues (i.e. liver, kidney and lungs). The limit of quantitation (5 ng/ml) is substantially lower than currently published methods for the analysis of TCE in tissues. The % RSD and % Error for the assay falls within the acceptable range (<15% for middle and high QC points and <20% for low QC points), and the recovery is high from all tissues (>79%).

Quantitative bioreduction assays for calibrating spore content and viability of commercial Bacillus thuringiensis insecticides

The redox dyes MTT (3-{4,5-dimethylthiazol-2-yl}-2,5-diphenyl tetrazolium bromide, thiazolyl blue) and XTT (sodium 3′- {1-[(phenylamino)-carbonyl]-3,4-tetrazolium}-bis{4-methoxy-6-nitro} benzene sulphonic acid hydrate) were used as dosimetry reporters in liquid (multi-well) and solid support (membrane) assays to estimate spore viability and content of commercial BT products derived from fermentation of Bacillus thuringiensis subsp kurstaki (Btk) and subsp israelensis (Bti). QC tests on five BT products were done using spore, protein and gene contents, and morphology (scanning electron microscopy) as indicators. Spore levels (6–40 × 109 colony forming units (CFU) ml−1) were approximately equivalent when based on International Units (IU) of potency. Spore viability was highly stable over a broad range of temperatures and pHs but germination and growth were restricted (optima: pH ≈ 7.5 and 37°C). Quantitative bioreduction activity (QBA) of MTT and XTT correlated with vegetative cell production. Depending on manipulation of pre-assay conditions, both dyes could discriminate doses from ∼2 to 109 spores (or 10−3 to 106 IU). Non-toxic effects of XTT and its formazan product enabled automated collection of data on growth and dose. Solid support assays also reliably estimated product dosage by in situ detection of CFU. With appropriate reference dilutions of microbe-containing products the QBA assays can provide high throughput QC monitoring of product comparisons and field release in aerial spray or water injection applications.

Two-dimensional coda Q structure beneath Tohoku, NE Japan

Based on the single scattering model, coda-Q values (Qc) are estimated for several frequency bands from the time decay of coda wave amplitude. The Qc value shows a regional variation and frequency dependency of the form Qcαfn, where n is found to be 0.6–1.2. A method for estimating the 2–D Qc structure has been developed to investigate the regional variation of the Qc value beneath Tohoku, the NE part of Honshu, Japan. The Qc value at each grid point spatially distributed is estimated by averaging the observed Qc values for many event-station pairs with adequate weighting factors. The weighting factor at each grid point for an event-station pair is calculated by taking into account the amount of energy contribution to the coda wave from that grid point. The obtained 2-D Qc structure shows some relation to the S-wave velocity structure, the Qs structure and the seismic activity in this area. In general, low Qc regions have a tendency to correspond to the regions with low S-wave velocity, low Qs value and high seismic activity, while high Qc regions correspond to those with high S-wave velocity, high Qs value and low seismic activity. In the regions around active volcanoes and near the coast of the Japan Sea the Qc value is relatively low, whereas it is relatively high near the coast of the Pacific Ocean.

Time‐space variation of seismic S‐wave coda attenuation (Qc−1) and magnitude distribution (b‐values) for the Petatlan Earthquake

Average S‐wave coda‐Q (Qc) at 6 Hz and to about 10 sec after the S‐wave arrival shows: (1) temporal variation positively correlated with the magnitude distribution parameter b for foreshocks and aftershocks of the 1979 Petatlan, Mexico earthquake; (2) spatial variation through the aftershock area, positively correlated with b, high Qc ‐b values at the two activity centers, intermediate values in between and landward, and low values toward the Middle America Trench, which remain low for two weeks after the main shock; and (3) five‐foreshock average Qc = 135±1.6% and eleven‐aftershock average Qc= 175±1.3% for the eastern asperity. The b values—and possibly Qc values—seem to correlate with the level of aftershock activity.

High Temperature Strength and Stability of Oxide Dispersion Hardened Alloys

The creep behavior of oxide dispersed alloys can be described by the following equation:where ε is steady state creep rate, σ applied stress, R gas constant, T temperature in °K, Qc activation energy for creep, n stress exponent, A and n are constants.Two unusual observations in the case of O.D. alloys are that Qc and n take on values that have not been explained satisfactorily. This investigation was undertaken to explain the unusually high strength, high Qc and high stability (high value of n) in the oxide dispersed alloys.