Review Ho & Gao Key term
Biomarker: Characteristic that is objectively measured and evaluated as anindicator of normal biologic processes, pathogenic processes, or pharmacologicresponse to a therapeutic intervention.
selected one method based on the results of ‘extraction and purification efficiency’ [4]. Gu et al. detailed their efforts to optimize mass spectrometric and chromato- graphic conditions to improve sensitivity [10]. Wang and Korfmacher tested columns of different stationary phase material in order to retain the hydrophilic analyte on column [30]. Schmidt et al. elaborated the rationale of choosing liquid extraction over solid-phase extrac- tion [16]. Van Dam et al. optimized chromagraphic conditions using experimental design with the aid of JMP®
reported optimization of electrospray and mass spec- trometer conditions during method development [31,32]. Ahonen et al. included the precursor and product ion selection and signal optimization in their paper [15].
Method qualification (validation) & tiered approach The two frequently asked questions regarding surro- gate matrix tissue method qualification are what should be qualified and what guidelines to follow. Researchers are not always clear what experiments should be done with their limited time and resources to establish suf- ficient confidence in the analytical assay. Furthermore, there has not been a clear guideline from the regula- tory agency on required experiments and acceptance criteria for tissue method qualification. Yue et al. cited a collection of 17 sources as bioanalytical method vali- dation references for their experimental design, almost 29% of the total number of references cited [11]. This exemplifies the considerable time that has been spent trying to answer these two questions. Regarding what should be qualified, the general-
ized answer is fit-for-purpose. The concept of fit-for- purpose was presented by Lee et al. to address the issue of method validation for biomarker methods [33,34]. They argue that it is neither necessary nor feasible to perform full method validation for all biomarker anal- ysis. They suggested a tiered-approach, with which the extent of method validation is determined by the intended use of the data. The fit-for-purpose concept and tiered approach has been adapted by the bioanaly- sis community in general [35–37] and their applicabil- ity has extended beyond biomarker analysis. Xue et al. elaborated the tiered approach for tissue analysis [38]. The European Bioanalysis Forum made recommen- dations on tissue homogenate analysis based on the tiered approach [39]. Using the tiered approach, exten-
2424 Bioanalysis (2015) 7(18)
sive method qualification is not conducted at the drug discovery stage and a generic method can be used. The tissue homogenization conditions (e.g., homog- enizer, solvent, time, temperature and dilution fold) and homogenate extraction conditions are optimized using representative compounds and the optimized conditions are used for multiple studies. As the lead compound moves toward late discovery and develop- ment stage, more exhaustive method qualification may be needed (Figure 1). The surrogate matrix approach is well-suited for
8.0.1 software (SAS Institute Inc.) [7]. Zacs et al.
discovery stage tissue analysis. Since plasma samples are collected with the tissue samples in most studies, Chen et al. evaluated the possibility of using plasma as surrogate matrix for tissues [19]. They found when 3× tissue homogenate of heart, tumor, brain, lung, spleen, liver and muscle are diluted by plasma for at least ten- fold (sample contains 90% plasma and 3.3% tissue), the resulting samples can be quantified against the plasma curve and the results were within ±25% com- pared with the data generated using tissue. A similar approach has also been used for development drugs. Jiang et al. reported quantification of plasma diluted tissue homogenate against the plasma curve [20]. They found the 5× tissue homogenate had to be diluted with plasma for at least fivefold (sample contains 80% plasma and 4% tissue) in order to yield accurate results when quantifying against the plasma curve. The dif- ference between Jiang and Chen’s methods is that the plasma method used by Jiang was fully validated. The qualification of a surrogate matrix method can
be considered as a process that consists of two parts: demonstrate surrogate matrix validity, that is, tissue samples can be quantified against a calibration curve in surrogate; and demonstrate method validity in surro- gate matrix. The method qualification parameters and the kinds of stability evaluation for surrogate matrix tissue methods are listed in Tables 2 & 3, respectively. When the same surrogate matrix is used for multiple tissues, the tissue related stability evaluation has to be performed for each tissue. Tables 2 & 3 indicate that sur- rogate matrix method qualification is about double the work compare to the matching matrix method qualifi- cation. This should be kept in mind when qualifying a surrogate matrix method for tissue analysis. Examples of comprehensive method qualification
using surrogate matrix approaches can be found in the work of Teunissen et al. [27] and O’Brien et al. [17]. It is rare that all the experiments listed in Tables 2 & 3 are performed. Key parameters that many researchers eval- uate during the method qualification include: linearity in surrogate matrix, and sensitivity, precision, accuracy, recovery, and certain kinds of stability in surrogate and tissue [3–4,7,11,13,16,23,28]. Besides the aforementioned
future science group
Page 1 |
Page 2 |
Page 3 |
Page 4 |
Page 5 |
Page 6 |
Page 7 |
Page 8 |
Page 9 |
Page 10 |
Page 11 |
Page 12 |
Page 13 |
Page 14 |
Page 15 |
Page 16 |
Page 17 |
Page 18 |
Page 19 |
Page 20 |
Page 21 |
Page 22 |
Page 23 |
Page 24 |
Page 25 |
Page 26 |
Page 27 |
Page 28 |
Page 29 |
Page 30 |
Page 31 |
Page 32 |
Page 33 |
Page 34 |
Page 35 |
Page 36 |
Page 37 |
Page 38 |
Page 39 |
Page 40 |
Page 41 |
Page 42 |
Page 43 |
Page 44 |
Page 45 |
Page 46 |
Page 47 |
Page 48 |
Page 49 |
Page 50 |
Page 51 |
Page 52 |
Page 53 |
Page 54 |
Page 55 |
Page 56 |
Page 57 |
Page 58 |
Page 59 |
Page 60 |
Page 61 |
Page 62 |
Page 63 |
Page 64 |
Page 65 |
Page 66 |
Page 67 |
Page 68 |
Page 69 |
Page 70 |
Page 71 |
Page 72 |
Page 73 |
Page 74 |
Page 75 |
Page 76 |
Page 77 |
Page 78 |
Page 79 |
Page 80 |
Page 81 |
Page 82 |
Page 83 |
Page 84 |
Page 85 |
Page 86 |
Page 87 |
Page 88 |
Page 89 |
Page 90 |
Page 91 |
Page 92 |
Page 93 |
Page 94 |
Page 95 |
Page 96 |
Page 97 |
Page 98 |
Page 99 |
Page 100 |
Page 101 |
Page 102 |
Page 103 |
Page 104 |
Page 105 |
Page 106 |
Page 107 |
Page 108 |
Page 109 |
Page 110 |
Page 111 |
Page 112 |
Page 113 |
Page 114 |
Page 115 |
Page 116 |
Page 117 |
Page 118 |
Page 119 |
Page 120 |
Page 121 |
Page 122 |
Page 123 |
Page 124 |
Page 125 |
Page 126 |
Page 127 |
Page 128 |
Page 129 |
Page 130 |
Page 131 |
Page 132 |
Page 133 |
Page 134 |
Page 135 |
Page 136 |
Page 137 |
Page 138 |
Page 139 |
Page 140 |
Page 141 |
Page 142 |
Page 143 |
Page 144 |
Page 145 |
Page 146 |
Page 147 |
Page 148 |
Page 149 |
Page 150 |
Page 151 |
Page 152 |
Page 153 |
Page 154