The use of LC MS/MS may be of importance in this regard, since all three laboratories that were able to measure the lowest samples used some form of that technique for their assays. Mandel��s h and k statistic analyses were consistent with minimal bias for the fortified pools and with relatively minimum assay selleck compound variance among the laboratories. Two laboratories had very small but statistically significant biases for one or two pools in the study. Several laboratories had assay variances that were significantly greater than the pooled variance for one or occasionally two pools in the study; however, in only two cases were these differences of potential concern. In the case of Laboratory 1-A, this increased variance was associated with the lowest concentration fortified pool that was relatively close to the LOD for that laboratory��s method; thus, greater variability might be expected.

The reason for the relatively greater variance in the other case (Pool D in Laboratory 7) was not apparent. However, as indicated in Table 4, even in that case, the relative standard deviation remained only 7.5%. Assay sensitivity requirements may vary according to the intended applications. For studies involving the active use of tobacco, all the laboratories and methods used in this work were capable of excellent results. However, in the United States and other developed nations around the world, the capability of measuring even quite low concentrations of serum cotinine in nonsmokers is becoming more important as the incidence and intensity of exposure of nonsmokers to SHS decline.

For example, in the third National Health and Nutrition Examination Survey, Phase 1, which covered the period 1988�C1991, the median serum cotinine concentration for nonsmokers in the United States was 0.204 ng/ml among adults aged 20 years and older and 0.262 ng/ml for children aged 4�C11 years. By 2001�C2002, the median concentration among nonsmoker adults had declined to 0.034 ng/ml and it had declined to 0.067 ng/ml among children (Pirkle et al., 2006). When the incidence and intensity of exposure to SHS are high, a relatively high cutpoint is needed to exclude most nonsmokers. However, as the incidence and intensity of exposure to tobacco smoke continue to decline, the serum cotinine cutoff level between active smokers and nonsmokers exposed to SHS can also be expected to decline (Benowitz et al., 2009). Detecting and stratifying exposures at these declining concentration levels require sensitive and precise methodology. The results of this investigation Dacomitinib confirm that with the use of modern methodology, excellent agreement in measurements can be achieved among different laboratories.