Review Ho & Gao Key terms
Authentic matrix: Control matrix used for calibration samples that closely match the study samples, that is, the same type of tissue, from same species and homogenized in the same way.
Surrogate matrix: Substitute matrix used to prepare calibration standards that is devoid of the target analyte and suitably depicts the behavior of the biological sample matrix.
However, using surrogate matrix for tissue analysis
also presents great challenges. The major challenges are introduction of potential risks of data inaccuracy and increase of the time and cost of method estab- lishment. The matrix differences between surrogate matrix and incurred samples present potentially higher risks of data inaccuracy compared with the matching tissue method. For example, there may be an interfer- ence that is unique to surrogate matrix or tissue, which may affect the quantitation. Furthermore, the extract- ability, recovery, matrix effects and stability of analyte in surrogate matrix and in tissue may differ, leading to inaccurate results. Establishing a surrogate matrix method requires more time and effort compared with a method using matching tissue. The validity of sur- rogate matrix needs to be evaluated, which is an addi- tional task relative to the matching matrix method. Many method parameters, including recovery, matrix effects and stability must be evaluated in both surro- gate matrix and matching tissue (Tables 2 & 3) to sub- stantiate the method, adding work. Another frequently encountered challenge is lack of control matching tis- sues. With surrogate matrix methods, it is possible to perform sample analysis without any matching tissue. However, matching tissue is needed for method estab- lishment. This is somewhat paradoxical considering one of the major reasons for using a surrogate matrix method is the lack of or limited availability of match- ing tissue. In many cases, method performance evalua- tions are restricted to selected parameters based on the
Study samples Standard QC
Blank
Total samples Total curves
Authentic 3 × 8 = 24
amount of control tissue available. When there is no control tissue available, certain method parameters can be evaluated using incurred tissues. Due to the challenges identified, surrogate matrix
approaches generally should not be the first choice for tissue analysis. When possible, tissue should be quanti- fied against calibration curve prepared in matching tis- sue. However, a surrogate matrix approach is a valuable option for tissue analysis because of the opportunities it offers in some circumstances. There has not been a review article on surrogate matrix tissue methods, nor any consensus or guidelines for method validation and sample analysis for tissue analysis. The information that is available is scattered among diverse sources. This makes it difficult to know the best approach for establishing a surrogate matrix tissue method. The purpose of this article is to begin to address this
deficiency. We present criteria for selecting a proper sur- rogate matrix and methods for validating a surrogate matrix. We discuss the challenges and considerations for method development, qualification and tissue sam- ple analysis when a surrogate matrix tissue method is used. We also summarize the analytical approaches for evaluating assay parameters including sensitivity, spec- ificity, selectivity, precision, accuracy, recovery, matrix effects and stability. The authors hope this article helps investigators make more informed decisions regarding the use of surrogate matrix for tissue analysis and to properly manage the challenges while leveraging the opportunities available with this approach.
Surrogate matrix for tissue analysis Selecting proper surrogate matrix Various matrices including water, buffer, solvent, mixture of solvent/aqueous, plasma, whole blood, tis- sue and artificially prepared or modified matrix have been used as the surrogate for tissue sample analysis. The ideal surrogate matrix should be suitable, avail- able and affordable. The suitable surrogate matrix is free of analyte and is identical to the tissue in terms
Table 1. Illustration of efficiency improvement using surrogate matrix approach. Sample
Surrogate (discovery) 3 × 8 = 24
16 × 8 = 128 6 × 8 = 48 2 × 8 = 16 216 8
16 (in surrogate) 0 2
42 1
16 (in surrogate)
6 × (8 + 1) = 54 (in tissues and surrogate) 2 × (8 + 1) = 18 112 1
Assumption: single dose is administered at 1 dose level. There are three animals in the group and eight different tissues per animal are collected. There are total 24 tissue samples, 3 samples/tissue. Bioanalysis samples: calibration curve: eight levels in duplicate (16 standard samples); QC: three levels in duplicate (6 QC samples), blank (IS only): two samples.
Surrogate (development) 3 × 8 = 24
2420
Bioanalysis (2015) 7(18)
future science group
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