Quality control:

Can be defined as a part of quality management focused on fulfilling quality requirements. While quality
assurance relates to how a process is preformed or how a product is made QC is more the inspection of
quality management

Quality assurance:
Can be defined as a part of quality management focused in providing confidence that quality
requirement will be fulfilled that confidence provided by quality assurance is twofold internally to
management and external to customers, government , agencies ,regulators and certifiers .

Sampling, transport, traceability and storage of laboratory samples.

Sampling:

Take primary samples randomly with a lot of method of sampling must be recorded.

Transport:

Samples must be transported under appropriate conditions in clean containers

Rapid transport to the laboratory preferably

Traceability

Samples must be identified clearly and indelibly each laboratory sample must be allocated a unique code
storage:

Should be stored under conditions that minimized decay.

Sample preparation and processing

Sample processing and storage procedures should have been demonstrated to have no significant effect
on the residues present in the sample

Ambient temperature has a significant influence on degradation of certain pesticide residues.

It is recommended that small particle sizes, performed in away that avoids extensive heating of the
samples.

Sample communication should ensure that the sample is homogenous

Pooling of sample:

An option for analytes with low frequency pesticide residues

Provided that detection system is sensitive enough when pooling 5 samples LOQ must be at least 5 times
lower than the reporting limit RL .

Extraction conditions and efficiency:

Samples containing incurred residues can be analysed using varying extraction condition to obtain
further information on extraction efficiency
Number of parameters such as samples processing temperature, PH , time , etc can affect extraction
efficiency and analyte stability.

Addition of water to samples prior to extraction is recommended

Clean up concentration / reconstitution and storage of extracts:

Clean up dilution step may necessary to reduce matrix interference and reduce contamination

Concentration of sample extracts can cause precipitation of matrix component similarly , dilution of the
extract with a solvent of a different polarity can also result in pesticide losses due to decrease solubility.

To avoid losses during evaporation steps temperature should be kept as low as is practicable .

Analyte stability in extracts should be evaluated during method validation. Storage of extracts
refrigerator or freezer will minimize degradation .

Calibration for Quantification :

External standards:

The most commonly employed standardization uses one or more external standards known
concentration of analyte .these are identified as external standard as they prepared and analysed
separately from the samples.

Multiple point external standardization is accomplished by constructing a calibration curve , this is the
most frequently employed method of standardization , the resulting relationship often called normal
calibration curve when the calibration curve is linear.

Standard additions:
The complication of matching the matrix of the standards to that of sample can be avoided by conducting the
standardization in the sample .

Since a standard additions calibrations curve is constructed in the sample , it can not be extended to the analysis of
another sample .

Internal standards :
a chemical compound added to the sample test portion or sample extract in known quantity at a specific stage of
the analysis in order to check the correct execution of the analytical method , the internal standard should be
chemically stable and/ or typically show the same behavior as the target analysis.

Since the analyte internal standard in any sample or standard receive the same treatment , the ratio of their signal
will be unaffected by any lack of reproducibility in the procedure.

Limit of Detection (LOD) :

Generally defined as the lowest amount of an analyte in an sample that can be detected by a particular analytical
method or

It is the lowest amount of substance that can be distinguished from the absence of substance (zero point ) with a
stated confidence level .
Limit of quantification :
It gives the smallest concentration of an analyte in a test sample that we can determine with acceptable
repeatability and accuracy.

Proficiency testing :
Is to help laboratories detect and cure any unacceptably large inaccuracy in their reported results.

Validation:
All the developed analytical methods need to be validated to make sure that each measurement of the content of

the analyte in the sample in routine analysis is close to the true values. There are international guidelines for

validation of the analytical methods including FDA European Medicines Agency (EMA) ,International Union of the

Pure and Applied Chemistry (IUPAC) and Association of Oicial Analytical Chemists (AOAC) International .

Matrix efect (ME):

ME measurement is necessary for validation when the analytical method uses mass spectrometry as the detector

due to the ion suppression or induction caused by the matrix components. The ME evaluation required spiking the

analyte (at low and high concentrations) in six lots of matrix obtained from individual donors.

Robustness:
As defined by USP ,robustness measures the capacity of an analytical method to remain unaffected by small but
deliberate variations in method parameters , robustness provides some indication of reliability of an analytical
method during normal usage .

Identifying uncertainty sources :

1-sampling

2-storage condition ( duration of storage as well as condition during storage)

3- instrumental effects ( limits of accuracy on the calibration of an analyte balance , temperature controller)

4- reagent purity (concertation of volumetric solution )

5- Assumed stoichiometry

6- measurement conditions ( volumetric glassware may be used at an ambient temperature different from that at
which calibration )

7- sample effect ( recovery of analyte from a complex matrix )

8- computational effects ( selection of calibration model as straight line calibration leads to poor fit a higher
uncertainty – round off can lead to inaccuries in final result )

9-blank correction

10- operature effect

11- random effects

Analytical methods validation:

1- Linearity
Acceptable criteria (the correlation coefficient for six concentration levels will be ≥ 0.999)

2- Range
Acceptable criteria ( precision of ≤ 3 % RSD )

3- Accuracy
Acceptable criteria ( the mean recovery will be within 90% to 110 % of optical value for non-regulated

Products 100 ± 2% is typical for an assay of an active ingredient)

4- Precision – repeatability
Acceptable criteria (RSD should be 1 % for drug substance )
5- Intermediate precision

Acceptable criteria ( the assay results by two operators using two instrument on different days should
have a statistical RSD ≤ 2 % )

6- Limit of Detection
Acceptable criteria (HC recommends a signal-to-noise ratio 3 : 1 )
7- Limit of Quantification
Acceptable criteria ( described as the concentration that gives a signal-to-noise ratio (a peak with height at
least ten times as high as the baseline noise level of 10:1 , HC states that LOQ is best estimate of low
concentration that gives an RSD approximately 10% for minimum of six replicate determination )

8- System suitability
Acceptable criteria ( retention (K) should be ≥ 2.0 resolution RS should be ≥ 2 between the peak of
interest and closest eluted peak , RSD will be 1 % for six injections , tailing factor should be 2 ,
theoretical plates (N) ≥ 2000 ).