Drug substance or a finished
(drug) product
Content uniformity
Dissolution testing
Impurity
80 to 120 % of the test concentration
70 to 130 % of the test concentration
+/-20 % over the specified range
1 to 120% of the specification

.
Accuracy: The degree to which an experimental result approaches the true or accepted answer
Accuracy – nearness to the truth

Error: The difference between the result obtained by a method and the true or accepted value.
Absolute Error d = (X – µ)
𝐗 − µ
𝐑𝐞𝐥𝐚𝐭𝐢𝐯𝐞 𝐞𝐫𝐫𝐨𝐫 % =
µ = the true result
𝐗
µ
𝐱 𝟏𝟎𝟎
µ
𝐱 𝟏𝟎𝟎
All Methods, except counting, contain errors – don’t know “true” value

 Atomic absorption analysis of As +3 and pb +2 in a sample yield the following results
As +3 = 600 µg.ml
-1 d = 5 µg. ml -1 pb +2 = 9 µg.ml
-1 d = 0.3 µg.ml
-1
From absolute error As +3 results is less accurate than pb +2 results but is not true as we see from relative error.
E rel As +3 = 5/600 x100 =0.83%
E rel pb +2 = 0.3/9 x100 = 3.3 %
As +3 results is more accurate, although it has larger absolute error.

Several methods of determining accuracy are available:
Drug Substance
(authentic sample)
Drug Product
(formulation)
Impurities
(Quantitation)
1. Application to an analyte of known purity (e.g.
reference material);
2. Comparison with those of a second wellcharacterized procedure, the accuracy of which is stated and/or defined. (Reference methods)
1. Application to synthetic mixtures of the drug product components to which known quantities of the drug substance to be analyzed have been added;
2. In cases where it is impossible to obtain samples of all drug product components, it may be acceptable either to add known quantities of the analyte to the drug product or to compare the results obtained from a second, well characterized procedure, the accuracy of which is stated and/or defined
Accuracy must assessed on samples spiked with known amount of impurities

 Using a minimum of 9 determinations over a minimum of 3 concentration levels covering the specified range (e.g. 3 concentrations /3 replicates each of the total analytical procedure).
 Accuracy should be reported as percent recovery

 Precision: The degree to which an experimental result varies from one determination to the next.
Precision - reproducibility

1. Absolute Standard Division
If the results are normally distributed, 68.3 % of the results can be expected to fall within the range of ± 1 σ of the mean as a result of random error.

2. Relative Standard deviation:
3. Confidence limits
We might use this to estimate the probability that the population mean (µ) lies within a certain region centered at
X

A pharmacist determined the % of vitamin C in Rino C
Tablets, obtaining the following results,
= 15.3 σ = 0.1 n= 4
Calculate the confidence limit of the mean at probability90% and 99% (t =2.353 at 90 % probability and, 5.841 at probability 99%)
Solution
µ = 15.3 ± 2.353 x 0.1/√4 µ = 15.3 ± 0.12
µ = 15.3 ± 5.841 x 0.1/√4 µ = 15.3 ± 0.29

Repeatability should be assessed using: a) A minimum of 9 determinations covering the specified range for the procedure (e.g. 3 concentrations/3 replicates each) or b) A minimum of 6 determinations at 100% of the test concentration.
Recommended Data:
The standard deviation, relative standard deviation
(coefficient of variation) and confidence interval should be reported for each type of precision investigated.

Chromatogram of the same concentration of
Norfloxacin; (a) 5 mg% and the same concentration of
Salicylic acid, (d) 2 mg% id at 274 nm.

Sensitivity
• Limit of detection (LOD) – “the lowest content that can be measured with reasonable statistical certainty.”
نيقيلا نم ةلوقعم ةيئاصحإ
• Limit of quantitative measurement (LOQ) –
“the lowest concentration of an analyte that can be determined with acceptable precision (repeatability) and accuracy under the stated conditions of the test.”
How low can you go?

Detection Limit
 smallest concentration which can be reported with a specified degree of certainty by a definite, complete analytical procedure.

(depending on whether the procedure is a noninstrumental or instrumental.)
 Based on:
1. Visual Evaluation
2. Signal-to-Noise
3. The Standard Deviation of the Response and the
Slope a) the Standard Deviation of the Blank b) the Calibration Curve

 Based on Visual Evaluation
Is determined by the analysis of samples with known concentrations of analyte and by establishing the minimum level at which the analyte can be reliably detected.
 Signal-to-Noise
Typically 3 times the signal-to-noise (based on standard deviation of the noise) تاجوم لخادت

 The Standard Deviation of the Response and the Slope
The detection limit (DL) may be expressed as:
DL = 3.3 σ/S
• σ = the standard deviation of the response
• S = the slope of the calibration curve
• The slope S may be estimated from the calibration curve of the analyte. The estimate of
σ may be carried out in a variety of ways, for example:
– Based on the Standard Deviation of the Blank
– Based on the Calibration Curve

 The minimum level at which the analyte can be quantified with acceptable accuracy and precision.

 Based on Signal-to-Noise Approach
Typically 10 times the signal-to-noise (based on standard deviation of the noise)
 Based on the Standard Deviation of the Response and the Slope
The quantization limit (QL) may be expressed as:
QL = 10σ/ S
Where s= the standard deviation of the response
S = the slope of the calibration curve
The slope S may be estimated from the calibration curve of the analyte.
 The slope S may be estimated from the calibration curve of the analyte.
The estimate of σ may be carried out in a variety of ways, for example:
– Based on the Standard Deviation of the Blank
– Based on the Calibration Curve

 Robustness of an analytical procedure is a measure of its capacity to remain unaffected by small but
deliberate variations in method parameters. It should show the reliability during its usage.
 Examples of typical variations are:
1. stability of analytical solutions,
2. extraction time.
Examples In the case of liquid chromatography,
1. variations of pH in a mobile phase
2. variations in mobile phase composition,
3. different columns (different lots and/or suppliers),
4. temperature,
5. flow rate.
In the case of gas-chromatography, examples of typical variations are different columns, temperature, flow rate.

 Ruggedness of an analytical method is the degree of reproducibility of the results obtained by the analysis of the same sample under a variety of normal test conditions.
For example different
 laboratory,
 analysts,
 instruments, and
 reagents.

• The tests are based on the concept that the equipment, electronics,
analytical operations and samples to be analyzed constitutes an integral system that can be evaluated as such.
وحنلا اذه ىلع همييقت نكمي لماكتم ماظن لكشيو