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the key elements of interest, as cited in ICH Q3D (Class 1 and 2A). The count rates of the detected x-rays are pro- portional to the concentration in the irradiated sample. Quantitative applications can be created by analyzing a set of known standards of analytes in the concentration ranges of interest. Typically this is done for a specific matrix type. Unlike ICP techniques, XRF methods do not need daily recalibration. In most cases, a monthly drift check using known samples reveals whether the calibra- tion is within specification. Traditionally, preparation of solid XRF samples involves grinding the material to a homogeneous particle size and compressing the powder into a solid pellet using a 10- to 30-ton press. The photo below shows a typical 5- gram pellet 40 millimeters (mm) in diameter. With no fur- ther preparation needed, the sample is simply placed into the designated cup and analyzed. While this two-step method is simpler than having to digest samples, it could be improved. In fact, we have developed and tested a method in which the analyst simply pours finished tablets into a cup and analyzes them. In the photos below, a set of oblong tablets and a whole pellet (for comparison) are ready for WD-XRF analysis. We describe the new method of analysis and its advantages below. Methods Equipment. All quantitative analyses were performed using a Rigaku WD-XRF Primus IV, which operates at 4 killowatts at maximum power, with tube-above optics and a SuperTrace 30-micron-thick beryllium (Be) end- window rhodium (Rh) tube. The instrument is equipped with scintillation counter (SC) and flow-proportional counter (F-PC) detectors. The power setting (killivolt- milliamp) was optimized to achieve maximum excitation of elements that ICH Q3D classifies as Class 1 and Class 2A, i.e., lead (Pb), arsenic (As), cadmium (Cd), mercury (Hg), cobalt (Co), vanadium (V), and nickel (Ni). Peak and background positions were chosen for efficient counting times. Table 1 lists the instrument's operating parameters during the analysis of these elements. Bulk powder mixing was done in a Retsch Mixer Mill E-MM-2000 (Premier Lab Supply, Port St. Lucie, FL). 28 March 2017 Tablets & Capsules Figure 2 Specificity: Qualitative heavy scans Figure 1 Generation of x-ray fluorescence 1. Primary x-rays strike inner-shell electrons. 2. An inner-shell electron is kicked out as a photoelectron. 3. An outer-shell electron transfers to fill the vacancy. 4. Fluorescent x-ray is emitted with equivalent energy difference. X-ray tube Fluorescent x-rays Primary x-rays Sample Kβ Primary x-rays M shell Kα Fluorescent x-rays Photoelectrons K shell L shell Lα 1 2 3 4 30 40 50 60 70 80 100 90 80 70 60 50 40 30 20 10 0 Intensity (kilo-counts per second) 2-theta angle (degrees) Typical 5-gram pellet 40 mm in diameter A set of oblong tablets and a pellet ready for analysis. The ability to test finished tablets simplifies the analysis. Table 1 Representative parameters of instrument in operation Parameter Element Hg-LA Cd-KA Pb-LB1 As-KA Co-KA V-KA Ni-KA Common conditions Emission line KA, LA, LB1 Tube target Rh Atmosphere Vacuum Meas. diameter (mm) 30 Spin setting On Primary beam filter Out (exceptions for Cd- Ni400; Hg, Pb, As - Al125) Component type Metals Balance C6H1005 (cellulose) Element-specific conditions Power (kV-mA) 50-70 60-60 50-70 50-70 50-70 50-70 50-70 Slit S2 S2 S2 S2 S2 S2 S2 Analyzing crystal LiF(220) LiF(220) LiF(220) LiF(220) LiF(220) LiF(220) LiF(220) Detector SC SC SC SC SC SC SC PHA setting 105-270 120-270 115-270 110-280 105-290 105-285 100-300 Peak angle (deg) 51.676 21.684 40.344 48.812 77.908 123.262 71.280 BG1 (deg) 51.240 21.320 40.040 48.240 77.380 122.240 72.140 BG2 (deg) 52.020 22.240 40.700 49.480 78.549 - - BG coefficient - - - - - - - Time - Peak (sec) 45 240 120 20 10 20 5 Time - BG (sec) 45/45 120/120 120/120 20/20 10/10 10 5