Contents

Radiochemistry Quality Control

Effective Date: 07/2008
Point of Contact: Quality Engineer for Regulatory Programs

Radiochemistry preparative techniques and radiochemistry analytical techniques are described below.

Radiochemical Preparative Techniques

For QC purposes, radiochemical preparative techniques are those processes used to alter the physical or chemical state of a sample to make it suitable for counting (or other instrumental analysis). Preparative techniques may include digestion, dissolution, extraction, and/or leaching of a sample material. Separation and/or isolation techniques are also considered preparative. Simple dilution is not considered a sample preparation technique. The Preparative and Analytical Requirements for Radiochemistry Quality Control exhibit provides frequency and acceptance criteria of radiochemical QC.

Batch

A batch is a group of samples, of similar matrix type, processed through the preparative techniques at the same time. For each batch, a set of preparative QC shall be processed. A batch shall not exceed 20 samples, excluding the preparative QC samples (e.g., PB, LCS, BS, MS, duplicate). If the client does not specify project-specific QC, the laboratory may combine up to 20 samples of similar matrix type for preparation with only one set of preparative QC. In the case of process testing or unique client requirements, QC elements such as a sample duplicate (or MSD) and MS may be performed for every 20 client-specific samples received. However, the PB and LCS or BS requirement would apply to each batch of samples prepared at one time. Unique client requirements shall be documented and agreed upon by the project and the client before work begins.

Tracer

A tracer is used to correct method performance in a specific sample. A tracer represents the addition to an aliquot of sample a known quantity of a radioactive isotope that is different from that of the isotope of interest but expected to behave the same. Radiochemical techniques typically employ either a tracer or matrix spike, or a combination of a MS with a tracer or carrier. Criteria for selection and recovery of tracers shall be specified in each method. Sample results are normally corrected based on tracer recovery.

The tracer may be added to an aliquot of prepared (e.g., leached), or diluted sample prior to specific radiochemical manipulations (e.g., separations). The tracer added at this point can indicate matrix-related effects remaining fter preparation but gives no measure of the efficiency of the original preparation step. The decision on when to spike a sample with tracer is based on the expected analyte activity in the sample. If the sample is relatively high in activity, tracer is typically added following original sample preparation.

Carrier

A carrier is used to correct method performance in a specific sample. A carrier represents the addition to an aliquot of sample a known quantity of stable element that is expected to behave the same as the isotope of interest. Criteria for selection and recovery of carriers shall be specified in each method as use may be considered unique to the specific isotope being determined. Sample results are normally corrected based on the yield recovered on a carrier. Radiochemical techniques typically employ a matrix spike or tracer or a combination of a matrix spike with a tracer or carrier.

The carrier may be added to an aliquot of prepared (e.g., leached) sample prior to specific radiochemical manipulations (e.g., separations). The carrier added at this point can indicate matrix-related effects remaining after preparation but gives no measure of the efficiency of the original preparation step. The decisions on when to spike a sample with carrier is based on the expected analyte activity in the sample. If the sample is relatively high in activity, carrier is typically added following original sample preparation.

Note, high yields in radiochemistry are not always of great importance, provided that the yields can be evaluated (i.e., it is common to sacrifice yield to achieve a better separation). Before applying a yield correction, evaluations of whether or not sufficient counting statistics were achieved to make yield correction meaningful shall be made.

Preparation Blank

The sample PB is used to monitor contamination resulting from the sample preparation. The PB is generally deionized water, or appropriate reagent, which is subjected to the same processing as the samples, including all reagent additions. A matrix more closely related to the actual samples processed may be used provided the matrix is free of contamination from analytes of interest. The PB initial volume or weight shall be approximately equal to the initial sample weight or volume being processed.

Laboratory Control Sample or Blank Spike

The laboratory control sample (LCS) or blank spike (BS) is used to monitor the effectiveness of the sample preparation process. A laboratory control sample is a material similar in nature to the sample being processed containing the isotope(s) of interest (e. g., standard reference material). A laboratory control sample, if available, shall be prepared with each batch of samples processed at the same time. The blank spike is distilled or deionized water or other suitable substrate spiked with the isotope(s) of interest. A blank spike is normally used when an appropriate laboratory control sample is unavailable.

The decision on when and how to introduce an LCS/BS into an analytical batch may be based on the anticipated sample analyte activity or required dilution. For samples that exhibit high activity, introduction of an LCS/BS at the initiation of sample preparation is not justifiable, either because of standard material consumption or radiation dosimetry issues. Likewise, a large subsequent dilution can waste expensive standard material. Therefore, an LCS/BS may be introduced after preliminary sample preparation and dilution, but before any radiochemical separation occurs. In these cases,it is acknowledged that the LCS/BS is monitoring only the effectiveness of the separation, purification, and counting process rather than the entire sample preparation process.

The blank, spiked with tracer meets the BS/LCS requirement. Laboratory control sample or blank spike control is demonstrated by target analytes being within established control or tolerance limits. Control limits are statistically determined by multiple analyses over time. Tolerance limits are established by the DQO process or as defined in Table 8.8 as 80 to 110% yield-corrected recovery. For the LCS, the vendor supplied precision may effect the tolerance limits applied to the analyte. All samples in the preparation batch shall be re-prepared and re-analyzed for those analytes when one of the acceptance criteria for the LCS or BS has not been met for the analyte. The laboratory control sample/blank spike results shall be reported to the client. No adjustment of client sample results based on LCS recovery is make in the laboratory report.

Matrix Spike

In general, a matrix spike is a client sample that has been spiked with the analyte(s) of interest and processed in the same manner as the sample. The matrix spike is used to monitor method performance in a specific sample matrix. Matrix spike results are a measure of the accuracy in the measurement of the target analytes introduced by the client sample matrix.

In radiochemistry, the matrix spike represents the addition of a known quantity of the isotope of interest to an aliquot of sample. Radiochemical analysis may include a matrix spike added to an aliquot of the sample prior to any sample preparation (i.e., fusion, leaching) or prior to specific radiochemical manipulation (e.g., separation chemistry or evaporation onto a planchet). The decision when to spike a sample is based on the expected analyte activity level present in the sample. Spiking additional activity into a sample that already exhibits high activity is not justifiable. In such cases, spiking is generally performed after preliminary sample preparation, but before any additional sample handling except large dilution. However, activity levels in such cases should always exceed the decision or action limit. Radiochemical techniques typically employ either a matrix spike or tracer, or a combination of a matrix spike with a carrier or tracer.

There is currently no capability to reliably perform a MS on fusion preparations. Additionally, a MS is typically not performed with sample batches of high activity. When such capability becomes available it shall be incorporated into relevant procedures.

The project shall evaluate matrix spike recovery information against client data quality requirements. The goal is to ensure that limitations on the data caused by the sample matrix and represented by matrix spike performance, are adequately portrayed and discussed in the report to the client.

When the analyte concentration is unknown, spiking is typically performed at a level that is one of the following: 1) equivalent to the threshold established by the DQO process, 2) specified by method, or 3) 1 to 5 times the minimum detectable activity. Otherwise, (as general guidance) the spiking should be performed at a level equivalent to 1.0 to 5 times that of the sample. In those instances where the analyte concentration significantly exceeds the amount of spike added in the prepared samples, the data must be further evaluated to determine if the count rate of the spiked sample is statistically significant.

For radiochemical analysis, matrix spike control is demonstrated when target analytes are within established control limits. Control limits are established by one of the following: 1) established by the client via the DQO process, or 2) laboratory performance over time in samples of similar matrix and concentration levels.

A matrix spike shall be prepared with each batch of 20 samples and the results reported to the client along with the calculated recovery. No adjustment of the client sample results is made in the laboratory report.

Sample Duplicate or Matrix Spike Duplicate

Laboratory duplicates are two aliquots of the same sample (intralaboratory splits) that are taken through the entire sample preparation and analytical process. MSDs are two spiked aliquots of the same sample that are taken through the entire sample preparation and analytical process. Duplicates are used to assess the precision of the preparation process for a specific matrix. Although more replicates can be requested, typically duplicates are required as a minimum. Precision is estimated by calculating the RPD. To the degree possible, the project and the client should agree upon the use of sample duplicates versus MSDs before starting work. A duplicate or MSD shall be prepared with each batch of samples of similar matrix.

Typically, radiochemical preparations include a sample and sample duplicate in those instances where a high probability exists that the analyte(s) of interest will be detected in the sample. In cases where the sample is not expected to contain reasonable concentrations of any analyte of interest, it would be prudent to employ a MS and MSD.

Radiochemical laboratory duplicates should agree with an RPD of < 20% when the two results are > 5 times the MDA or the individual uncertainties are < 20%. Or alternately, the duplicates should agree within 2 standard deviations (mean difference less than 1.96). The formula for calculating the MD is presented in the Common Data Quality Calculations section of this plan.

Post-Digestion Spike

A spike performed after initial sample preparation (e.g., fusion, digestion, leach) is considered a post digestion spike. This spike can indicate matrix-related effects remaining after preparation, but gives no measure of initial sample preparation adequacy.

Radiochemical Analytical Techniques

The Preparative and Analytical Requirements for Radiochemistry Quality Control exhibit provides frequency, acceptance criteria, and corrective action requirements of radiochemical QC.

Analytical Run or Sequence

An analytical run or sequence is defined as those samples counted on any specific detector in a period of time between counter control counts. The analytical run starts after the counter control source is counted and ends when the following counter control source is counted. The sequence of samples counted on a detector where the detector face is directly exposed to the sample shall be traceable.

Verification of Calibration

The calibration verification confirms the acceptability of the calibration. The calibration verification demonstrates that both the standards used and the calibration are accurate. Calibration verification shall be performed before beginning sample analysis.

Calibration of counting instrumentation used in support of radiochemical measurements often applies over an extended period of time (e. g., years). Only one calibration verification needs to be performed after instrument calibration per geometry. Instrument stability, and thus calibration stability, is monitored by a counter control source (the equivalent of a CCV.

The concept of calibration verification is accomplished in radiochemistry by use of independent standards, use of independent measurements, multiple calibration curves, and/or data analysis. Examples of these concepts are provided below.

Use of independent standard

An independent standard is prepared in the same geometry as the calibration standard. Standards prepared from a separate lot from the calibration standard is acceptable. The measured activity from the calibration verification standard shall fall within acceptable tolerance limits (as defined in the governing standard operating procedure).

Use of independent measurement

The calibration standard is measured on an independently calibrated detector for confirmation of the isotope activity. This will confirm the standard was prepared correctly and will provide an accurate basis for the calibration.

Multiple calibration curves

Multiple calibration curves are often generated during instrument calibration(s) from multiple standard preparations (e. g., attenuation curves for multiple detectors, efficiency curves for multiple geometries). The data for these calibrations shall be evaluated for consistency.

Data analysis

Multiple radioisotopes are used to calibrate gamma spectrometers. The calibration curve generated shall be evaluated for smoothness of fit of the gamma energy to the counting efficiency. Gamma calibration curves shall be linear at higher energies (varies by detector and matrix) when plotted on a log-log scale.

Counter Control Source

The counter control source is used to monitor instrument stability over time. Acceptable performance confirms that the instrument is in control and the calibration is still valid. The control source should provide adequate counting statistics over the time period for which the source is to be counted. However, the source shall not be so radioactive as to cause: 1) pulse pileups, 2) dead time that is significantly different from that expected from routine samples, or 3) gain shift in the case of pulse height analyzer systems. The standard used for the control source does not need to meet the same traceability requirements as the standards used for calibration.

If the counter control source result is outside the control limits, then the counter control source shall be counted a second time. If the counter control source is inside the control limits, then the analytical sequence proceeds. If the counter control source is outside the control limits after the second count, then the system shall be considered out of control. Investigation shall be performed to determine the source of the out of control condition. Corrective action shall be taken, and the counter control source recounted. All samples run since the last acceptable counter control source shall be investigated.

Backgrounds

Background count rate is a measure of system and/or environmental contributions and is a fundamental aspect of the minimum detectable activity (MDA) determination. Background counts are determined periodically. Background counts are normally subtracted from all subsequent sample counts.