Surrogate matrices

The nse of surrogate matrices was a major concern in biomedical analyses in the context of quantitation of endogenous analytes, bnt this particular problem was solved recently by an ingenious approach (Li 2003a Jemal 2003) discussed in Section 11.7. 

---

In some cases a suitable control matrix may not be available, e.g., soils from different sources around the world (and thus widely variable). In some cases it may be necessary to resort to use of a matrix containing known analyte concentrations that lie well below the LLOQ required for the particular analysis at hand, or analyte-stripped or surrogate matrices (Section 9.4.7c), but all of these approaches are problematic and may require additional vahdation procedures. Unavailability of a truly blank matrix was until very recently a major intrinsic problem in quantitation of endogenous analytes but novel new procedures have been recently developed for this particular application (Section 11.7). 

FIGURE 5.89. Illustration of the difference between PCR and PLS. The major difference between the methods is how the surrogate matrix (U) is calculated. 

For analytes that have endogenous levels, standards can be prepared in treated or surrogate matrix. Comparison of responses of spiked analyte in the standard matrix versus the sample matrix should be performed to demonstrate the lack of matrix effects. 

This has been a subject of much discussion and debate. Many assay kits will be provided with calibration standards that have been prepared in a surrogate matrix. One example is protein-based buffer solution. 

Surrogate matrix calibration standards also mean that many methods can be used across many matrices (and even species) as long as the matrix-specific investigations are done via the experiments mentioned above and described in more detail later. This is why many approved diagnostic methods will be found with matrix specificity data for plasma containing different anticoagulants as well as serum or other biological fluids. 

Surrogate matrix spiked with molecule of interest sourced from a third party suppber... 

Surrogate matrix spiked with cahbration standard material... 

Preparing the running QC surrogates, matrix spikes, and, in some cases, matrix spike duplicates per batch of samples. A batch is defined in EPA methods to be approximately 20 samples. These reference standard spikes serve to assess extraction efficiency where applicable. Matrix spikes and duplicates are often required in EPA methods. 

Before sample preparation, surrogate compounds must be added to the matrix. These are used to evaluate the efficiency of recovery of sample for any analytical method. Surrogate standards are often brominated, fluorinated, or isotopically labeled compounds that are not expected to be present in environmental media. If the surrogates are detected by GC/MS within the specified range, it is... 

Continuing calibration for a Series Method is performed using calibration check compounds. Surrogate compounds are added to the matrix before sample preparation to evaluate recovery levels. To check GC retention times, internal standards are added to a sample after its preparation for analysis. 

It is also important to note that matrix-related effects, either signal enhancement or more commonly signal suppression, can have a pronounced effect on quantitative measurements. Based on these observations, the use of isotope-labeled standards is helpful to achieve accurate analytical measurement data on the diastereoisomers. Several methods found in the open literature include use of both 13C-labeled and d18-labeled surrogates as recovery and/or instrument standards [118],... 

M [8]. Ferguson et al. [10] have shown that matrix effects may result in severe ion suppression in APEO analysis (this phenomenon occurs particularly in negative mode electrospray ionisation). They also demonstrated that the effect may be accounted for appropriately when using internal and surrogate standards, which closely mimic the ionisation behaviour of the analytes. In Ferguson s study, specially... 

Internal quality control is undertaken by the inclusion of particular reference materials, called control materials , into the analytical sequence and by duplicate analysis. The control materials should, wherever possible, be representative of the test materials under consideration in respect of matrix composition, the state of physical preparation and the concentration range of the analyte. As the control materials are treated in exactly the same way as the test materials, they are regarded as surrogates that can be used to characterise the performance of the analytical system, both at a specific time and over longer intervals. Internal quality control is a final check of the correct execution of all of the procedures (including calibration) that are prescribed in the analytical protocol and all of the other quality assurance measures that underlie good analytical practice. IQC is therefore necessarily retrospective. It is also required to be as far as possible independent of the analytical protocol, especially the calibration, that it is designed to test. 

Soxhlet, sonication, supercritical fluid, subcritical or accelerated solvent, and purge-and-trap extraction have been introduced into a variety of methods for the extraction of contaminated soil. Headspace is recommended as a screening method. Shaking/vortexing is adequate for the extraction of petroleum hydrocarbons in most environmental samples. For these extraction methods, the ability to extract petroleum hydrocarbons from soil and water samples depends on the solvent and the sample matrix. Surrogates (compounds of known identity and quantity) are frequently added to monitor extraction efficiency. Environmental laboratories also generally perform matrix spikes (addition of target analytes) to determine if the soil or water matrix retains analytes. 

One method that is often nsed for method validation is the addition of a surrogate to the sample matrix, then following the track of the surrogate through the separation procedure. It is appropriate at this point, to comment on such a procedure. 

Jemal, M., Schuster, A., and Whigan, D. B. (2003). Liquid chromatography/tandem mass spectrometry methods for quantitation of mevalonic acid in human plasma and urine method validation, demonstration of using a surrogate analyte, and demonstration of unacceptable matrix effect in spite of use of a stable isotope analog internal standard. Rapid Commun. Mass Spectrom. 17, 1723-1734. 

Quality Assurance/Quality Control. QA/QC measures included field blanks, solvent blanks, method blanks, matrix spikes, and surrogates. Percent recovery was determined using three surrogate compounds (nitrobenzene-d5, 2-fluorobiphenyl, d-terphenyl-diQ and matrix spikes (naphthalene, pyrene, benzo[ghi]perylene) the recoveries ranged from 80 to 102%. Separate calibration models were built for each of the 16 PAHs using internal standards (naphthalene-dg, phenanthrene-dio, perylene-di2). Validation was performed using a contaminated river sediment (SRM 1944) obtained from NIST (Gaithersburg, MD) accuracy was <20% for each of the 16 analytes. 

If no such (certified) reference materials are available, a blank sample matrix of interest can be spiked with a known amount of a pure and stable in-house material, called the spike or surrogate. Recovery is then calculated as the percentage of... 

For environmental analyses in which the matrix varies from sample to sample, the analysis of a surrogate gives a warning if a particular sample is not behaving as expected fashion. As with all QC materials, there must be criteria for the acceptance of surrogate analyses. When there is more than one surrogate, whether all or some fail the criteria is a useful diagnostic. If... 

Buprenorphine, the other option for transdermal application on account of its potency, is more difficult to apply dermally in therapeutic doses (Roy et al., 1994 Grond et al., 2000). A surrogate parameter for skin penetration, provided the other prerequisites are fulfilled (Fig. 7), is the melting point of the active substance. With buprenorphine base this is 209°C and about 260°C for buprenorphine hydrochloride, compared with, for example, 83°C for fentanyl base and 150°C for fentanyl dihydrogen citrate. The DDS developer LTS devised a technical solution for reliable transdermal buprenorphine administration in the form of a matrix patch (Fig. 9). 

The reduction schemes used by Tang et al. [20] to define the surrogate fewer state system follows the method proposed by Shore [62]. The scheme has a compact form when we introduce two orthogonal projection operators P and Q and work in the frequency domain instead of the time domain. The time evolution matrix for the n-state system dynamics, U(f). and its Fourier transform, G(w), satisfy the following equations ... 

Spike blanks, samples and standards, ready for extraction with surrogate standard. Spike each calibration standard matrix with appropriate amount of standard for the calibration curve standards and each QC sample. Vortex the standard curve samples and QC samples for approximately 5 sec. 

---