A Simple Protein Precipitation-based Simultaneous Quantification of Lovastatin and Its Active Metabolite Lovastatin Acid in Human Plasma by Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry using Polarity Switching.

Lovastatin is an anti-cholesterol lactone drug indicated for the treatment of hyperlipidemia and to reduce the risk of coronary heart disease. It is converted to the ß-hydroxy acid form (lovastatin acid) in vivo, which is the major pharmacologically active metabolite. Here, we describe the development and validation of an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS)-based method utilizing polarity switching for the simultaneous quantification of lovastatin and lovastatin acid in human plasma. Simple protein precipitation extraction and direct injection of the extracted samples without drying/reconstitution showed good recoveries of both analytes (~70%). The developed method exhibited satisfactory intra-day and inter-day accuracy and precision. The interconversion between lovastatin and lovastatin acid during sample preparation and storage was minimal (< 1.9%). The lower limits of quantification were 0.5 and 0.2 nM (or 0.2 and 0.084 ng/mL) for lovastatin and lovastatin acid, respectively, using only 50 µL of plasma during extraction. The validated method was successfully applied to analyze plasma samples obtained from a healthy human subject who enrolled in a clinical drug interaction study involving lovastatin.

Surface and superficial dose dosimetric verification for postmastectomy radiotherapy.

In patients given postmastectomy radiotherapy (PMRT), the chest wall is a very thin layer of soft tissue with a low-density lung tissue behind. Chest wall treated in this situation with a high-energy photon beam presents a high dosimetric uncertainty region for both calculation and measurement. The purpose of this study was to measure and to evaluate the surface and superficial doses for patients requiring PMRT with different treatment techniques. An elliptic cylinder cork and superflab boluses were used to simulate the lung and the chest wall, respectively. Sets of computed tomography (CT) images with different chest wall thicknesses were acquired for the study phantom. Hypothetical clinical target volumes (CTVs) were outlined and modified to fit a margin of 1-3 mm, depending on the chest wall thickness, away from the surface for the sets of CT images. The planning target volume (PTV) was initially created by expanding an isotropic 3-mm margin from the CTV, and then a margin of 3 mm was shrunk from the phantom surface to avoid artifact-driven results in the beam-let intensity. Treatment techniques using a pair of tangential wedged fields (TWFs) and 4-field intensity-modulated radiation therapy (IMRT) were designed with a prescribed fraction dose (D(p)) of 180 cGy. Superficial dose profiles around the phantom circumference at depths of 0, 1, 2, 3, and 5 mm were obtained for each treatment technique using radiochromic external beam therapy (EBT) films. EBT film exhibits good characteristics for dose measurements in the buildup region. Underdoses at the median and lateral regions of the TWF plans were shown. The dose profiles at shallow depths for the TWF plans show a dose buildup about 3 mm at the median and lateral tangential incident regions with a surface dose of about 52% of D(p). The dose was gradually increased toward the most obliquely tangential angle with a maximum dose of about 118% of D(p.) Dose profiles were more uniform in the PTV region for the 4-F IMRT plans. Most of the PTV region had doses >94% of D(p) at depths >1 mm. The mean surface dose was about 65% of D(p) for the 4-F IMRT plans. The maximum dose for the 4-F IMRT plans was <118.4% of D(p). The application of added bolus has to consider the treatment technique, tumor coverage, and possible skin reactions. For PMRT, if the chest surface and wall are treated adequately, at least 3 mm bolus should be added to the chest wall when tangential beams and 6-MV photon energy are arranged. However, when the surface and superficial regions are not high-risk areas, an IMRT plan with tangential beams and 6-MV photon energy can provide uniform dose distributions within the PTV, spare the skin reaction, and deliver sufficient doses to the chest wall at depths >1 mm.

Dosimetric verification of surface and superficial doses for head and neck IMRT with different PTV shrinkage margins.

PURPOSE: Dosimetric uncertainty in the surface and superficial regions is still a major concern for radiation therapy and becomes more important when using the inverse planning algorithm for IMRT. The purpose of this study was to measure dose distributions and to evaluate the calculation accuracy in the superficial region for different planning target volume (PTV) shrinkage methods for head and neck IMRT plans. METHODS: A spherical polystyrene phantom 160 mm in diameter (ball phantom) was used to simulate the shape of the head. Strips of superflab bolus with thicknesses of 3.5 and 7.0 mm were spread on the surface of the ball phantom. Three sets of CT images were acquired for the ball phantom without and with the bolus. The hypothetical clinical target volume (CTV) and critical structures (spinal cord and parotid glands) were outlined on each set of CT images. The PTVs were initially created by expanding an isotropic 3 mm margin from the CTV and then margins of 0, 3, and 5 mm were shrunk from the phantom surface for dosimetric analysis. Seven-field IMRT plans with a prescribed dose of 180 cGy and same dose constraints were designed using an Eclipse treatment planning system. Superficial doses at depths of 0, 3.5, and 7.0 mm and at seven beam axis positions (gantry angles of 0 degrees, 30 degrees, 60 degrees, 80 degrees, 330 degrees, 300 degrees, and 280 degrees) were measured for each PTV shrinkage margin using 0.1 mm ultrathin thermoluminescent dosimeters. For each plan, the measured doses were compared to the calculated doses. RESULTS: The PTV without shrinkage had the highest intensity and the steepest dose gradient in the superficial region. The mean measured doses for different positions at depths of 0, 3.5, and 7.0 mm were 106 +/- 18, 185 +/- 16, and 188 +/- 12 cGy, respectively. For a PTV with 3 mm shrinkage, the mean measured doses were 94 +/- 13, 183 +/- 8, and 191 +/- 8 cGy. For a PTV with 5 mm shrinkage, the mean measured doses were 86 +/- 11, 173 +/- 8, and 187 +/- 5 cGy. The comparisons indicated that more than 73.3% of the calculated points are with doses lower than the measured points and the difference of the dose becomes more significant in the shallower region. At 7.0 mm depth, the average difference between calculations and measurements was 2.5% (maximum 5.5%). CONCLUSIONS: Application of the PTV shrinkage method should take into account the calculation inaccuracy, tumor coverage, and possible skin reaction. When the tumor does not invade the superficial region, an adequate shrinkage margin from the surface is helpful for reducing the skin reaction. As the tumor invades the superficial region, adding a bolus is a method better than only contouring PTV with skin inclusion.

Dosimetry of a novel rotating gamma system for stereotactic radiosurgery.

This is the first report of the basic dosimetric properties of a new rotating gamma system: the RGS Vertex360™. Dosimetric properties were compared to those measured with traditional rotating gamma systems and with the Leksell Gamma Knife. The RGS Vertex360 is similar to the original rotating gamma system developed by OUR New Medical Technology Development Co., Ltd. (Shenzen, China), however, there are a few notable differences including the angular arrangement of the sources. Basic dosimetric properties of the RGS Vertex360 were measured including: absorbed dose rate, output factors, mechanical and radiation center accuracy and dose profiles. A significant discrepancy was observed for the 4 mm output measured from the RGS Vertex360 compared to those obtained from previous rotating gamma units: the 4 mm output from the RGS Vertex360 (0.807) was 32-38% higher than those measured from previous units. This is somewhat surprising considering the excellent agreement in 4 mm outputs from the RGS Vertex360, the corresponding outputs specified by the manufacturer of the original OUR unit and those measured for the Leksell Gamma Knife. The mechanical accuracy was similar to previous rotating gamma systems while the 50-90% penumbra was narrower. Dose profiles compared favorably with the Leksell Gamma Knife: in many instances the measured penumbra was narrower for the RGS Vertex360. Notwithstanding the 4 mm output factor, the dosimetric properties of the RGS Vertex360 compared favorably with those of previous rotating gamma systems. The 4 mm output discrepancy was attributed to suboptimal alignment of the primary and secondary collimators in previous studies. The dosimetric properties of the RGS Vertex360 and the Leksell Gamma Knife were similar and, taken together, the results suggest that the new rotating gamma system is well suited for stereotactic radiosurgery procedures.

Development of improved free-air ionisation chamber as absolute dosimetry standard for low-energy X rays in INER.

The National Radiation Standard Laboratory of the Institute of Nuclear Energy Research (INER) designed and constructed an improved Attix style free-air ionisation chamber (FAC) for low-energy X-ray measurements. Clinically, X rays in this energy range are used in mammography radiology. This chamber is also used to perform air-kerma measurements. The original Attix two-sectional design was redesigned by INER using the piston design. The correction factors were determined experimentally for volume estimation, ion recombination and air attenuation. The aperture transmission, wall transmission, electron loss and photon scatter correction factors were determined using Monte Carlo calculations. INER established the Bureau International des Poids et Mesures (BIPM) X-ray beam code and performed a comparison of secondary standard air-kerma calibration factors for 10-50 kV low- energy X rays to verify the experimental accuracy and measurement consistency of the improved chamber. The INER-NMIJ/National Institute of Advanced Industrial Science and Technology (AIST) experimental results comparison using a transfer chamber yielded a difference <1.0% at the 95% confidence level in calibration factors. The overall uncertainty for the X-ray measurement in terms of air kerma was <0.6% at the 95% confidence level. These results indicated that the improved FAC is capable of serving as a primary standard as well as a trace standard in low-energy X-ray calibration services in Taiwan and even forming a basis for the future mammography X-ray air-kerma primary standard.