Accuracy carryover

It is recommended that OQ test the following on an HPLC system flow accuracy, pump compositional accuracy, pressure pulsations, column oven temperature accuracy/stability, detector noise/drift and wavelength accuracy, autosampler injection precision and carryover. 

Pump flow rate accuracy and gradient accuracy Detector linearity of response, noise, drift, and wavelength accuracy Injector precision, linearity, and carryover Column heater temperature accuracy... 

It would be worthwhile to consider that evaluation of the interference is performed through quantification of the interfering compound at a level below the LLOQ (criteria < 20%, i.e., outside the validated quantification range). Outside this range the accuracy of the results produced is unknown. The same considerations can be used for evaluation of the method carryover (see Section 8.3.7). 

Even if a reconstitution solvent blank is normally used to evaluate carryover during validation and sample analysis, it is suggested to use all three types of blank as mentioned earlier for carryover evaluation during the method development. As considered previously (see Section 8.3.2) in the quantitative evaluation of carryover, linearity of detection together with sufficient accuracy and precision below LLOQ should be assumed. This assumption is questionable, and for this reason some bioanalytical laboratories have chosen different criteria to evaluate the carryover. 

Cross validation is needed on a method that has been received from other institution or between sites of the same institution. This is to verify ability of the current laboratory to perform the assay. Most of the time, it requires three precision and accuracy runs. The evaluations of carryover, recovery, and the ability to dilute may be excluded if there is reason to believe these parameters will not be affected. Some or all of the stability evaluations may be excluded if the stability determinations have been adequately evaluated elsewhere and documentation of stability is available. 

This chapter provides an overview of modern HPLC equipment, including the operating principles and trends of pumps, injectors, detectors, data systems, and specialized applications systems. System dwell volume and instrumental bandwidth are discussed, with their impacts on shorter and smaller diameter column applications. The most important performance characteristics are flow precision and compositional accuracy for the pump, sampling precision and carryover for the autosampler, and sensitivity for the detector. Manufacturers and selection criteria for HPLC equipment are reviewed. 

Operational specifications Pump precision of retention time <0.5% RSD Composition accuracy <1% absolute Detector noise, <+2.5 x 10"5 AU Auto sampler precision <0.5% RSD, <0.1 carryover System dwell volume <1 mL Instrumental bandwidth <40 pL (4o)... 

Small-molecule quantification by automated infusion using the ESI Chip has been demonstrated to be able to provide comparable precision, accuracy and linear dynamic range compared to traditional LC-MS-MS.28 32 A linear dynamic range greater than five orders of magnitude was demonstrated which enabled validation of bioanalytical assays without the carryover limitations of LC-MS.32... 

Polymeric microfluidic systems coupled to a microfabricated planar polymer tip can be used as a stable ion source for ESI-MS. A parylene tip at the end of the microchannel delivers fluid which easily produces a stable Taylor cone at the tip via an applied voltage. The described device appears to facilitate the formation of a stable spray current for the electrospray process and hence offers an attractive alternative to previously reported electrospray emitters. When this interface was employed for the quantification of methylphenidate in urine extracts via direct infusion MS analysis, this system demonstrated stable electrospray performance, good reproducibility, a wide linear dynamic range, a relatively low limit of quantification, good precision and accuracy, and negligible system carryover. We believe polymeric devices such as described in this report merit further investigation for chip-based sample analysis employing electrospray MS in the future. 

Most manufacturers provide some indication of the performance of their analyzers with preferred reagents in terms of imprecision, linearity, and reportable ranges. All analytical methods should be assessed by the user for imprecision, accuracy, linearity, limits of detection, and carryover between samples. 

Urdike any other traditional GC injection methods (e.g., solvent injection using a traditional syringe), carryover effect plays an ingiortant role in SPME/GC analysis. If the thermal desorption time is not properly chosen, the con unds remaining on the SPME fiber lead to poor accuracy and precision in SPME/GC analysis. 

Manual injectors are operationally qualified for repeatability and carryover. Autosamplers are additionally checked for accuracy. Injection systems are qualified after the solvent dehvery system and the detector. To eliminate subjective effects, the chromatographic column is excluded from the setup for qualifying injectors. The column is replaced by a low internal diameter, significant length stainless steel tubing, generating a pressure drop similar to that in a packed column (about 100 bar). 

The method should be assessed using the same or similar calibration standards, QCs and blanks that will be used for validation. In addition to a final assessment of sensitivity, linearity, accuracy and precision, additional experiments designed to assess analyte stability during the sample preparation and analysis processes, method robustness and ruggedness, carryover, and potential... 

For study sample analysis the calibration curve and QC samples are evaluated separately, and run acceptance is based upon criteria estabhshed for both curves and QCs. For validation runs, however, only the standard curve and other factors such as carryover are considered for run acceptance and aU of the results for the various types of validation QCs, e.g., precision and accuracy, stability, etc., are reported and used for statistical analysis. It is important at this time to emphasize the distinction between a failed and rejected validation run. Runs may be rejected for specific assignable cause such as documented evidence that the method was run incorrectly or hardware failure (Section 10.5.2c). Data from failed runs on the other hand, such as those where an excessive number of calibrators are considered to be outhers or QCs used to assess precision and accuracy do not meet the... 

The fundamental components of a bioanal5dical validation (and aU validations in general) are selectivity sensitivity accuracy precision range of reliable response and linearity and reproducibility. Other characteristics of the method that should be addressed are stability carryover and control of lab contamination and matrix effects, including interferences from metabolites in incurred samples or other co-extracted compounds, as well as ionization suppression. 

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