Interbatch precision

A variety of xanthines including caffeine, theobromine, and theophylline have been found from food materials including.coffee, chocolate, and tea (419-420). Theophylline determination in sera has been much studied. The technique allows the determination of theophylline at serum levels of 1.5-20 mg/liter theophylline with sample sizes ranging from 50 to 10 /xl (42 -425). Hill (426) assayed theophylline using 50 /xl of serum and an analysis time of 8 min with good interbatch precision and accuracy. Alternative methods which allow the determination of as little as 0.1 mg/ml (427) or 20 ng theophylline in 10 ml serum have been described (428). 

Between-run, interbatch precision or intermediate precision, which measures precision with time and may involve different analysts, equipment, reagents, and laboratories... 

Precision should be measured using a minimum of five determinations per concentration. A minimum of three concentrations in the range of expected concentrations is recommended. The precision determined at each concentration level should not exceed 15 % of the coefficient of variation (CV) except for the LLOQ, where it should not exceed 20 % of the CV. Precision is further subdivided into within-run, intrabatch precision or repeatability, which assesses precision during a single analytical run, and between-run, interbatch precision or reproducibility, which measures precision with time, and may involve different analysts, equipment, reagents, and laboratories. Since it is not always easy to obtain data about the reproducibility in the strict sense it often makes sense to use intermediate precision this expresses within-laboratories variations on different days, by different analysts, and on different equipment, etc. [60],... 

Acceptance criteria Part 1 Apply limits separately Part 2 Combined limit Calculated bias and precision satisfy 6a, 6b, 6c Bias %RE interbatch precision %CV <30 4-6-30 rule ... 

An LC-MS-MS method for simultaneous determination of metronidazole and spiramycin I concentrations in human plasma, saliva, and gingival crevicular fluid (GCF), preceded by liquid-liquid extraction (LLE). Omidazole is used as an internal standard. A C18 column is used with an eluent of acetonitrile, water, and formic acid. Intra- and interbatch precision 7, 12, and 9% in plasma, saliva, and GCF, respectively. Accuracy was lowest in saliva (15.4%) and better in plasma (8.7%) or in GCF (10.7%). Linearity, specificity, recovery, matrix effect, dilution process, stability in human plasma and saliva after three freeze-thaw cycles, stability in human plasma and saliva at ambient temperature, and stability of the extracts in the automatic injector of the HPLC system have been studied. Useful for pharmacokinetic evaluations. 

Table 8.1. Interbatch Accuracy and Precision for Gemcitabine and Its Deaminated Metabolite in Human Plasma Samples Diluted with Plasma versus Water...

For each in-study run, the standard curve must satisfy criteria described in the standard-curve section however, run acceptance is based primarily on the performance of the QC samples. When using total error for ligand binding assays of macromolecules, the run acceptance criteria recommended in the precision and accuracy section requires that at least four of six (67%) QC results must be within 30% of their nominal values, with at least 50% of the values for each QC level satisfying the 30% limit. The recommended 4-6-30 rule imposes limits simultaneously on the allowable random error (imprecision) and systematic error (mean bias). If the application of an assay requires a QC target acceptance limit different than the 30% deviation from the nominal value, then prestudy acceptance criteria for precision and accuracy should be adjusted so that the limit for the sum of the interbatch imprecision and absolute mean RE is equal to the revised QC acceptance limit. 

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