Changes In Detector Response Research Articles

JSI TRIGA fuel rod reactivity worth experiments for validation of Serpent-2 and RAPID fuel burnup calculations

Reactivity worth of fuel rods at the JSI TRIGA research reactor was measured. Differently burned fuel rods were chosen to validate fuel burnup calculations. Two methods of measuring reactivity worth of fuel rods are used, traditional method is compared to newly introduced method using fuel rods swapping. Connection between both methods is described theoretically and the theory is validated experimentally. Fuel rod worth calculated using the newly introduced fuel rod swap method was within 1σ of worth measured using the traditional method. In addition to the recently performed experiments, weekly measurements of reactor core reactivity throughout the operational history are used for validation. The measured data were used to validate the fuel burnup and core criticality calculations. Fuel burnup calculations are performed using three different computer codes: the deterministic TRIGLAV, the Monte Carlo Serpent-2, and the hybrid RAPID. Great agreement was observed for Serpent-2 and RAPID by simulating fuel rod worth and its burnup, indicating that the fuel burnup and criticality calculations are accurate and that reactivity changes due to small burnup differences on the order of 10 pcm can be accurately simulated. In addition it was shown using ex-core detectors and large fission chamber that detector response changes due to fuel swapping are evident for fuel rod burnup differences of 20 MWd/kg. Fuel burnup calculations were further validated on excess reactivity measurements for three mixed TRIGA cores. The calculated burnup reactivity coefficient ΔρBU using Serpent-2 and RAPID was within 1σ of the measurements, showing both codes are capable of calculating burnup for different TRIGA fuel types.

MR-guided ion therapy: Detector response in magnetic fields during carbon ion irradiation.

Combining carbon ion therapy with on-bed MR imaging has the potential to bring particle therapy to a new level of precision. However, the introduction of magnetic fields brings challenges for dosimetry and quality assurance. For protons, a small, but significant change in detector response was shown in the presence of magnetic fields previously. For carbon ion beams, so far no such experiments have beenperformed. To investigate the influence of external magnetic fields on the response of air-filled ionizationchambers. Four commercially available ionization chambers, three thimble type (Farmer, Semiflex, and PinPoint), and a plane parallel (Bragg peak) detector were investigated. Detectors were aligned in water such that their effective point of measurement was located at 2 cm depth. Irradiations were performed using square fields for carbon ions of 186.1, 272.5, and 402.8MeV/u employing magnetic field strengths of 0, 0.25, 0.5, and 1 T. In addition, the detector response for protons and carbon ions was compared taking into account the secondary electron spectra and employing protons of 252.7 MeV forcomparison. For all four detectors, a statistically significant change in detector response, dependent on the magnetic field strength, was found. The effect was more pronounced for higher energies. The highest effects were found at 0.5 T for the PinPoint detector with a change in detector response of 1.1%. The response of different detector types appeared to be related to the cavity diameter. For proton and carbon ion irradiation with similar secondary electron spectra, the change in detector response was larger for carbon ions compared toprotons. A small, but significant dependence of the detector response was found for carbon ion irradiation in a magnetic field. The effect was found to be larger for smaller cavity diameters and at medium magnetic field strengths. Changes in detector response were more pronounced for carbon ions compared toprotons.

Monte Carlo verification of output correction factors for a TrueBeam STx®

The recent publication of the new code of practice IAEA/AAPM TRS-483 introduces output correction factors to correct detector response changes in relative dosimetry of small photon beams. In TRS-483, average correction factors are reported for several detectors in high-energy photon beams at 6 and 10 MV with and without flattening filter. These correction factors were determined by Monte Carlo simulation or experimental measurements using several linacs of different brands and vendors. The goal of this work was to validate the output correction factors reported in TRS-483 for 6 MV photon beams of a TrueBeam STx® linac. The validation was performed using Monte Carlo simulations of four radiation detectors employed in the dosimetry of small photon beams and whose output correction factors were determined using a different radiation source than TrueBeam STx®. The results show that Monte Carlo calculated output correction factors, and those reported in the code of practice TRS-483 fully agree within ∼1%. The use of generic correction factors for a TrueBeam STx® and the detectors studied in this work is suitable for small field dosimetry static beams within the uncertainties of Monte Carlo calculations and output correction factors reported in TRS-483.

Benchmark on neutron flux spatial effects in subcritical system based on IRT-4 M fuel for near-core positions

The paper presents a benchmark aimed at assessing the accuracy of Monte Carlo codes to simulate the neutron detector response in near-core geometry of a subcritical water-moderated reactor. The experiment included six levels of subcriticality with keff from 0.93 to 0.996, and four fixed detector positions. Studied parameters included: first, the prediction of the change in detector response with the change in subcritical multiplication at a given detector position; second, the prediction of the change in neutron flux spatial distribution; third, the effectiveness of calculated correction factors to decrease the inconsistency in reactivity determined using detectors at various locations. Calculations were performed in MCNP6 code using two nuclear data sets. Both the general source and the eigenvalue (criticality) mode of calculation were studied. Finally, the effect of the offset between the calculated and experimentally determined critical condition on the prediction of detector response in the subcritical state was analysed.

Evaluation of dosimetric parameters of small fields of 6 MV flattening filter free photon beam measured using various detectors against Monte Carlo simulation

AbstractPurpose:This study aims to evaluate dosimetric parameters like percentage depth dose, dosimetric field size, depth of maximum dose surface dose, penumbra and output factors measured using IBA CC01 pinpoint chamber, IBA stereotactic field diode (SFD), PTW microDiamond against Monte Carlo (MC) simulation for 6 MV flattening filter-free small fields.Materials and Methods:The linear accelerator used in the study was a Varian TrueBeam® STx. All field sizes were defined by jaws. The required shift to effective point of measurement was given for CC01, SFD and microdiamond for depth dose measurements. The output factor of a given field size was taken as the ratio of meter readings normalised to 10 × 10 cm2 reference field size without applying any correction to account for changes in detector response. MC simulation was performed using PRIMO (PENELOPE-based program). The phase space files for MC simulation were adopted from the MyVarian Website.Results and Discussion:Variations were seen between the detectors and MC, especially for fields smaller than 2 × 2 cm2 where the lateral charge particle equilibrium was not satisfied. Diamond detector was seen as most suitable for all measurements above 1 × 1 cm2. SFD was seen very close to MC results except for under-response in output factor measurements. CC01 was observed to be suitable for field sizes above 2 × 2 cm2. Volume averaging effect for penumbra measurements in CC01 was observed. No detector was found suitable for surface dose measurement as surface ionisation was different from surface dose due to the effect of perturbation of fluence. Some discrepancies in measurements and MC values were observed which may suggest effects of source occlusion, shift in focal point or mismatch between real accelerator geometry and simulation geometry.Conclusion:For output factor measurement, TRS483 suggested correction factor needs to be applied to account for the difference in detector response. CC01 can be used for field sizes above 2 × 2 cm2 and microdiamond detector is suitable for above 1 × 1 cm2. Below these field sizes, perturbation corrections and volume averaging corrections need to be applied.

On-orbit radiometric calibration of Suomi NPP VIIRS reflective solar bands using the Moon and solar diffuser.

Radiometric calibration of the Suomi National Polar-orbiting Partnership Visible Infrared Imaging Radiometer Suite (VIIRS) reflective solar bands relies mainly on the onboard solar diffuser (SD) observations. The SD reflectance degrades over time due to the exposure to solar ultraviolet radiation. The uncertainties embedded in characterizing the SD bidirectional reflectance distribution function (BRDF) directly affect the accuracy of sensor radiometric calibration coefficients, such as F-factors, which are proxies of detector gain. The Moon-based radiometric calibration provides an independent way of validating and correcting the SD-based calibration. This study focuses on the comparison of the long-term SD F-factors with lunar F-factors by using two independent lunar irradiance models, i.e., Miller and Turner (MT) model and the Global Space-based Inter-Calibration System Implementation of ROLO (GIRO) model. To monitor the long-term detector response changes, the lunar F-factor differences are matched to the SD F-factors by applying the best fit scaling factors. Overall, the two lunar F-factors agree well, within 2% of one sigma standard deviation in the reflective solar bands compared to the SD F-factors. The lifetime standard deviations of difference between the GIRO-based lunar and SD F-factors show better long-term match than that of MT-based lunar F-factors. The GIRO-based lunar F-factors show increasing differences over time in comparison with the SD F-factors especially for bands M1 to M4, which indicates the underestimation of the VIIRS detector degradation by SD F-factors for these bands. Using standard SD calibration method and the GIRO-based lunar model, long-term difference between the lunar and SD F-factors shows there are 1.6%, 1.3%, 1.0%, and 0.9% increases in lunar F-factor trend for bands M1 to M4 at the end of year 2015. To mitigate these time-dependent biases, NOAA Ocean Color (OC) group and NASA VIIRS characterization support team (VCST) developed lunar correction methods and applied them to their specific products. However, the amounts of band-dependent lunar corrections are not consistent between these two teams, especially in the short-wavelength bands from M1 to M4, depending on the versions of lunar models and SD F-factor calculation algorithms. Using the standard SD F-factor algorithm and the multi-agency endorsed GIRO model, we derived lunar correction factors based on the quadratic fits between the SD and lunar F-factors. The differences with the NOAA OC group and NASA VCST team are compared and described in this study.

Neutron Rem Detector Response Changes due to Activation of Components.

The relative response of neutron rem detectors has previously been shown to increase after prolonged exposure to a neutron flux. This increase has been referred to as the "soak factor." The cause of the increased response has been previously unexplained. This note reports on a search for the underlying cause of the increased response. Testing involved gamma-ray spectroscopy of activated neutron rem detector components and testing of instrument response at various rates of neutron flux and accumulated fluence. The proposed primary cause of the increased response is activation of copper in the brass collar at the fill end of the gas-filled detector tube. This component allows for attachment of the extension housing on the tube containing BF3 or He gas. Under a neutron flux, some of this copper activates to Cu. In addition, Mn was detected in activated components but does not seem to be a significant contributor to the detector response. Cadmium isotopes did not appear to be significant. The activated component causes an increase in indicated neutron dose rate due to decay photons from activated components. Photons normally have little impact on neutron rem detector readings because the electrical pulses produced in the probes are below the lower-level discriminator. However, the photon pulses do impact the overall count rate when they occur simultaneously with normally uncounted, lower amplitude, wall-effect neutron pulses.

Feasibility of dosimetry with optically stimulated luminescence detectors in magnetic fields

The objective of this study was to analyze the applicability of optically stimulated luminescence detectors (OSLDs) for dosimetry in magnetic resonance (MR) guided radiation therapy devices with focus on dose dependence and angular dependence on the magnetic field strength.Precise detectors for dosimetry in high magnetic fields for such devices are still subject to research. In contrast to ionization chambers, OSLDs contain no air cavities, such that only minor changes in detector response with increasing magnetic field strengths are expected.To study the behavior of OSLDs in magnetic fields, Al2O3:C detector packages were irradiated at a 6 MV linac in a water phantom, while magnetic fields between 0.0 T and 1.0 T were applied. In order to study the angular dependence, the OSLD packages were rotated around the vertical axis for three different magnetic field strengths (0.0 T, 0.5 T, 1.0 T). Additionally, the angular dependence was measured at a clinical 0.3 T 60Co device. The OSLDs were read out using a portable OSL reader and an automated Risø TL/OSL-DA-15 reader.Readout with the portable reader yielded package standard deviations of 1–2% and revealed no significant relation between dose response and magnetic field strength, while readout with the Risø reader resulted in standard deviations of only 1% and a significant decrease in response of −1.3% per T (95%-confidence interval: −1.9% to −0.7%). The angular dependence was not significantly influenced by the magnetic field. The small decrease in dose response supports the applicability of the OSL technique in MR-guided radiation therapy devices. We expect that no additional magnetic field correction factor has to be used when a calibration of the detectors in the magnetic field of such a device is performed.

Application of an adapted Fano cavity test for Monte Carlo simulations in the presence of B-fields

With the advent of MR guided radiotherapy the relevance of Monte Carlo radiation transport simulations in the presence of strong magnetic fields (B-fields) is increasing. While new tests are available to benchmark these simulation algorithms for internal consistency, their application to known codes such as EGSnrc, PENELOPE, and GEANT4 is yet to be provided. In this paper a method is provided to apply the Fano cavity test as a benchmark for a generic implementation of B-field effects in PENELOPE. In addition, it is investigated whether violation of the conditions for the Fano test can partially explain the change in the response of ionization chambers in the presence of strong B-fields.In the present paper it is shown that the condition of isotropy of the secondary particle field (Charged Particle Isotropy, CPI) is an essential requirement to apply the Fano test in the presence of B-fields. Simulations in PENELOPE are performed with (B = 0.0 T) and (B = 1.5 T) for cylindrical cavity geometry. The secondary particle field consists of electrons generated from a mono-energetic source (E = 0.5–4.0 MeV) with a uniform source density and different angular distributions; isotropic, mono-directional, and Compton. In realistic photon fields the secondary radiation field has a non-isotropic angular distribution due to the Compton process. Based on the simulations for the Compton angular distribution (non-CPI), the response change of the cavity model in a uniform radiation field in the presence of B-fields is investigated.For the angular distributions that violate the CPI condition and B = 1.5 T, the deviations from 1 are considerable, which emphasizes the requirement of CPI. For the isotropic angular distributions obeying this requirement, both the results for B = 0.0 T and B = 1.5 T shows deviations from the predictions for E ⩾ 1.5 MeV with values up to 1.0% for E = 4.0 MeV. Nevertheless, due to the high correlation in the deviation for B = 0.0 T and B = 1.5 T, the accuracy of the PENELOPE code for the simulation of the change in detector response in the presence of B-fields is within 0.3%. The effect of the B-field on the detector response for non-isotropic angular distributions suggests that violation of CPI is a major contribution to the response change of ionization chambers in the presence of B-fields.

Printable sensors for explosive detonation

Here, we report the development of an organic thin film transistor (OTFT) based on printable solution processed polymers and employing a quantum tunnelling composite material as a sensor to convert the pressure wave output from detonation transmission tubing (shock tube) into an inherently amplified electronic signal for explosives initiation. The organic electronic detector allows detection of the signal in a low voltage operating range, an essential feature for sites employing live ordinances that is not provided by conventional electronic devices. We show that a 30-fold change in detector response is possible using the presented detector assembly. Degradation of the OTFT response with both time and repeated voltage scans was characterised, and device lifetime is shown to be consistent with the requirements for on-site printing and usage. The integration of a low cost organic electronic detector with inexpensive shock tube transmission fuse presents attractive avenues for the development of cheap and simple assemblies for precisely timed initiation of explosive chains.

Poster — Thur Eve — 27: Flattening Filter Free VMAT Quality Assurance: Dose Rate Considerations for Detector Response

Introduction:Radiation detector responses can be affected by dose rate. Due to higher dose per pulse and wider range of mu rates in FFF beams, detector responses should be characterized prior to implementation of QA protocols for FFF beams. During VMAT delivery, the MU rate may also vary dramatically within a treatment fraction. This study looks at the dose per pulse variation throughout a 3D volume for typical VMAT plans and the response characteristics for a variety of detectors, and makes recommendations on the design of QA protocols for FFF VMAT QA.Materials and Methods:Linac log file data and a simplified dose calculation algorithm are used to calculate dose per pulse for a variety of clinical VMAT plans, on a voxel by voxel basis, as a function of time in a cylindrical phantom. Diode and ion chamber array responses are characterized over the relevant range of dose per pulse and dose rate.Results:Dose per pulse ranges from <0.1 mGy/pulse to 1.5 mGy/pulse in a typical VMAT treatment delivery using the 10XFFF beam. Diode detector arrays demonstrate increased sensitivity to dose (+./− 3%) with increasing dose per pulse over this range. Ion chamber arrays demonstrate decreased sensitivity to dose (+/− 1%) with increasing dose rate over this range.Conclusions:QA protocols should be designed taking into consideration inherent changes in detector sensitivity with dose rate. Neglecting to account for changes in detector response with dose per pulse can lead to skewed QA results.

MO‐E‐17A‐11: In‐Phantom Detector Response in a Kilovoltage X‐Ray Beam

Purpose:To investigate changes in detector response in a kilovoltage x‐ray beam as a function of depth in phantom.Methods:Detector response in a 120kVp x‐ray beam as a function of depth in a PMMA phantom was determined for a reference class Exradin A12 ionization chamber, an Exradin A1SL ionization chamber, TLD‐100 and EBT3 radiochromic film and normalized to a depth of 1cm. The output of each detector was referenced to the A12 ionization chamber reading to assess changes in detector response as a function of depth. The BEAMnrc, DOSxyz, and egs_chamber user codes of the EGSnrc Monte Carlo code were used to calculate the dose delivered to the detectors from an x‐ray source with similar beam quality to the one used in the measurements.Results:Changes in detector response relative to the A12 ionization chamber of 2%, 7%, and 14% for the A1SL, TLDs, and film, respectively, were observed with the larger changes in response occurring at larger depths. The Monte Carlo calculated changes in dose response showed less deviation, with the largest difference being within 2%.Conclusion:The Monte Carlo simulations show that doses delivered to the different detectors are quite similar, while measurements show that the detector output varies drastically. This indicates that the detector output per unit dose is changing with depth, most likely due to changes in the photon spectrum that occur because of scatter and attenuation of the primary beam. Because detector calibration is often performed at a single point in the kilovoltage energy range, the change in detector response needs to be considered when the measurement conditions differ from those of the calibration. This is of particular concern in computed tomography dose measurement, where calibrations are performed at shallow depths or in air, and measurements are made at deeper locations.

SU‐E‐T‐494: A MOSFET‐Based In‐Vivo Dosimetry System for MR Image‐Guided Radiation Therapy (MR‐IGRT)

Purpose:To determine if a MOSFET based in‐vivo dosimetry system can be used for patients undergoing MR‐IGRT.Methods:Standard and high sensitivity MOSFET detectors were used for in‐field and out‐of‐field measurements respectively. The systems were benchmarked and calibrated against a calibrated ionization chamber on a standard 6 MV linear accelerator, and then on the MR‐IGRT system. Known doses were delivered to a water phantom with the MOSFETs placed between the top of the phantom and underneath a layer of bolus and water equivalent plastic, using a 6 MV beam and a 6 0Co MR‐IGRT beam. The latter was performed with and without real‐time MRI‐guidance during the beam delivery (MRIGRT).Results:The in‐field dosimeter response was linear from 50‐500 cGy with little evidence of energy dependence or change in response due to the permanent static magnetic field of the MR‐IGRT system. The detector response varied by < 2% between 6 MV and 6 0Co without image guided delivery. The out‐of‐field dosimeter response was linear from 1‐50 cGy; however the detectors did display dose rate and energy dependence as the response varied by > 20% depending on distance from isocenter used during calibration. Therefore, to use the dosimeters for out‐of‐field measurements they must be calibrated out‐of‐field. Regardless of the detector orientation in the coronal plan, the response of the MOSFETs during MRI‐guided delivery increased by 5% due to induced currents from the dynamic magnetic field present with image guidance. During the MRI‐guided delivery, some loss in image quality was seen when the MOSFETs were present in the imaging plane. This was mitigated by using a handheld reader without a transmitting wireless receiver.Conclusion:A MOSFET‐based in‐vivo dosimetry system can be used for patients receiving MR‐IGRT; however the change in detector response due to the dynamic magnetic field requires a special calibration.

Determination of small field output factors and correction factors using a Monte Carlo method for a 1000 MU/min CyberKnife® system equipped with fixed collimators

A new formalism for small field dosimetry has been proposed (Alfonso et al., 2008) with the concept of an additional correction factor (kQclin,Qmsrfclin,fmsr) which accounts for possible changes in detector response with field size. The aim of this work was to evaluate the response of eight commercially available detectors, then to provide a set of correction factors for a 1000 MU/min CyberKnife® equipped with fixed collimators and to compare them with those obtained for the 800 MU/min CyberKnife® version.Measurements were performed on a 1000 MU/min CyberKnife® with several active detectors designed for small field dosimetry (two chambers (PTW 31014 and 31018), three high resolution diodes (PTW 60016, 60017 and Sun Nuclear EDGE), a natural diamond (PTW 60003)) and two passive dosimeters (Harshaw TLD-700 7LiF:Mg,Ti thermoluminescent micro-cube and EBT3 radiochromic films). The CyberKnife® as well as the diode detectors, the PinPoint chamber, the diamond and the LiF micro-cubes were modeled with the PENELOPE Monte Carlo code in order to calculate the output factors in a point-like voxel of water (OFMC,w). A set of kQclin,Qmsrfclin,fmsr correction factors for the active detectors investigated is provided for the 1000 MU/min CyberKnife® in order to be used with the new formalism. A difference up to 2.4%, 2.0 and 1.7% in the correction factor obtained for the two different CyberKnife® models is found for the PTW 60003, the PTW 60016 and the PTW 60017 respectively. Although this difference is small, we recommend using specific kQclin,Qmsrfclin,fmsr correction factors for the 1000 MU/min CyberKnife® when they are available.

Interceptor and Phantom Trials of EDNS at UPMC

University of Pittsburgh Medical Center (UPMC) installed an Emergency Department Notification System (EDNS) in one of its hospitals. The system, manufactured by Thermo Fisher Scientific (Thermo Fisher Scientific, Inc., 81 Wyman Street, Waltham, MA 02454), consists of four NaI(Tl) scintillation detectors, a 2.5 L PVT gamma counter, a 512 channels multi-channel analyzer, a system controller, and a database-monitoring server. We evaluated a portable Interceptor Interceptor™ hand-held detector (Thermo Fisher Scientific, Inc., 81 Wyman Street, Waltham, MA 02454) as part of the system for potential ambulancebased early detection and warning unit. We present the minimum detectable activity, distance, and isotope identification success rates along with the change in detector response to various radioisotope sources placed in a Rando® humanoid phantom. (The Phantom Laboratory. P.O. Box 511, Salem, NY 12865-0511 USA). The present paper reports these results.

Quantification and normalization of x-ray mammograms

The analysis of (x-ray) mammograms remains qualitative, relying on the judgement of clinicians. We present a novel method to compute a quantitative, normalized measure of tissue radiodensity traversed by the primary beam incident on each pixel of a mammogram, a measure we term the standard attenuation rate (SAR). SAR enables: the estimation of breast density which is linked to cancer risk; direct comparison between images; the full potential of computer aided diagnosis to be utilized; and a basis for digital breast tomosynthesis reconstruction. It does this by removing the effects of the imaging conditions under which the mammogram is acquired. First, the x-ray spectrum incident upon the breast is calculated, and from this, the energy exiting the breast is calculated. The contribution of scattered radiation is calculated and subtracted. The SAR measure is the scaling factor that must be applied to the reference material in order to match the primary attenuation of the breast. Specifically, this is the scaled reference material attenuation which when traversed by an identical beam to that traversing the breast, and when subsequently detected, results in the primary component of the pixel intensity observed in the breast image. We present results using two tissue equivalent phantoms, as well as a sensitivity analysis to detector response changes over time and possible errors in compressed thickness measurement.

SU‐E‐T‐12: Radiation Detector Responses to Applied Homogeneous Transverse and Parallel Magnetic Fields

To determine the relative dose response of a diamond detector and a ion chamber in a clinical photon beam within uniform magnetic fields, endeavoring to evaluate and refine reference dosimetry techniques for use in integrated MR-linac systems. The Monte Carlo code PENELOPE was used to model the structure and materials of the PTW60003 diamond detector and PR06 ion chamber in a 6MV beam in the presence of a homogeneous magnetic field. The magnetic field strength was varied from 0 to 1.5T, and both the parallel and transverse magnetic field orientations with respect to the beam central axis were simulated. The long axes of the detectors were oriented both perpendicular and parallel to the radiation beam direction for each magnetic field orientation. All simulations determined the detectors' signal in air. A small electromagnet was used to experimentally determine the detectors' response in transverse magnetic fields up to 0.2T to validate the simulations. The simulated response of both detectors matched to the experimental data within the estimation error. The relative response of PR06 and diamond detector varied up to ±8.5% (depending on chamber orientation) and >9% respectively with increasing transverse magnetic field strength. In contrast, both detectors were found to be relatively insensitive to the increasing magnetic fields irrespective of the detector orientation in parallel magnetic field. A maximum change of 2% in PR06 response was observed at 1.5T parallel magnetic field and in the parallel orientation of chamber. This work has significant impact on dosimetry protocols for integrated MR-linac systems, where detector response may be altered by the presence of a magnetic field. The need for a magnetic field dependent correction factor is strongly indicated for the transverse magnetic field cases, while such changes in detector response can be largely ignored in parallel magnetic fields < 1T. CIHR (Canadian Institutes of Health Research) - funding support Faculty of Medicine and Dentistry, University of Alberta - funding support.

Evaporative Light Scattering Detection Based HPLC Method for the Determination of Polysorbate 80 in Therapeutic Protein Formulations

An evaporative light scattering detection (ELSD) based high-performance liquid chromatography (HPLC) method is developed for the determination of polysorbate 80 (tween 80) in therapeutic protein formulations. The method is simple and overcomes the difficulties associated with specificity and sensitivity. The method is suitable for the quantitation of polysorbate 80 in the usual formulation range (0.01-0.1%) as well as in trace amounts ≥13 µg/mL. The analysis is based on the removal of protein first by solid-phase extraction using Oasis HLB cartridges followed by HPLC analysis using Inertsil ODS-3 C 18 column (4.6×150 mm, 5 µm) using reversed-phase conditions. The detector response changes exponentially with an increase in polysorbate concentration. A very good linear fit of log ELSD response against log polysorbate 80 concentration is observed. The specificity, sensitivity, precision, and accuracy of the method are suitable for the quantitation of polysorbate 80 in protein formulations.

A method for low volume and low Se concentration samples and application to paired cerebrospinal fluid and serum samples

The well-known beneficial health effects of Se have demanded the development of rapid and accurate methods for its analysis. A flow injection (FI) method with inductively coupled plasma mass spectrometry (ICP-MS) as a selenium-selective detector was optimized. Flow injection was carried out using a Knauer 1100 smartline inert series liquid chromatograph coupled with a Perkin Elmer DRC II ICP-mass spectrometer. For sample injection a Perkin Elmer electronic valve equipped with a 25 μL sample loop was employed. Before measurement, standards or samples were administered with 1 μg/L rhodium as internal standard for correction of changes in detector response according to changes in sample electrolyte concentration. The method characterization parameters are: LOD (3σ criterion): 26 ng/L, LOQ (10σ criterion): 86 ng/L, linearity: 0.05–>10 μg/L, r 2=0.9999, serial or day-to-day precision at 2 μg/L: 4.48% or 5.6%. Accuracy was determined by (a) recovery experiments (CSF spiked with 2 μg/L Se); (b) comparison of FI-ICP-MS measurement with graphite furnace atomic absorption (GFAAS) measurements of 1:10 diluted serum samples; (c) Se determination in urine and serum control materials. Recovery (a) was 101.4%, measurement comparison with GFAAS (b) showed 98.8% (5 serum samples, 1:10 diluted in the range of 0.5–1.3 μg/L, compared to GFAAS determination, which was set to 100%), and accuracy was 96.8% or 105.6% for the serum or urine control material. Analysis time per sample was short and typically below 2 min for the complete measurement, including sample introduction, sample-line purge and quadruplicate Se determination. This method was used to determine Se in cerebrospinal fluid (CSF) and plasma (here parallel to GFAAS) in 35 paired serum and CSF samples. Se determination gave values in the range of 42–130 μg/L for serum and 1.63–6.66 μg/L for CSF. The median for Se in 35 individual CSF samples was 3.28 μg/L, the mean (±SD) was 3.67 (1.35) μg/L, whilst for individual serum samples the median was 81 μg/L and the mean (±SD) was 85 (26) μg/L. When relating the paired Se concentrations of CSF samples to respective serum samples it turned out that Se-CSF (behind blood brain barrier (BBB)) is independent on Se-serum concentration (before BBB).

Investigation of analytical variation in metabonomic analysis using liquid chromatography/mass spectrometry

Sources of analytical variation in high-performance liquid chromatography/mass spectrometry (HPLC/MS), such as changes in retention, mass accuracy or signal intensity, have been investigated to assess their importance as a variable in the metabonomic analysis of human urine. In this study chromatographic retention and mass accuracy were found to be quite reproducible with the most significant source of analytical variation in the data sets obtained being the result of changes in detector response. Depending on the signal intensity threshold used to define the presence of a peak a sample component could be present in some replicate injections and absent in others within the same run. The implementation of a more sophisticated data software analysis package was found to greatly reduce the impact of detector response variability resulting in improved data analysis.