System Suitability - The RSD Requirement

1. System Suitability –RSD Requirement
Basic understanding of calculation, Current practice and regulatory requirement
C. P. SINGH
Research Scientist – ARD

2. Replicate injections of a standard preparation or other standard solutions are compared to ascertain
whether requirements for precision are met.
Unless otherwise specified in the individual monograph, data from five replicate injections of the
analyte are used to calculate the relative standard deviation (RSD), if the requirement is ≤2.0%;
data from six replicate injections are used if the RSD requirement is >2.0%.
System Suitability - RSD

3. %𝐑𝐒𝐃 =
𝐊𝐁 𝐧
𝐭 𝟗𝟎%, 𝐧 − 𝟏
For the assay in a drug substance monograph, where the value is 100% for the pure substance, and no
maximum RSD is stated, the maximum permitted %RSD is calculated for a series of injections of the
reference solution:
System Suitability - RSD
Where:
K is a constant (0.349);
B is the upper limit given in the definition of the individual
monograph − 100%;
n is the number of replicate injections of the reference
solution (3 ≤ n ≤ 6);
t90%,n−1 is the Student’s t at the 90% probability level
(double sided) with n−1 degrees of freedom.
RSD Requirement
B (%)
Number of individual injections
3 4 5 6
Maximum Permitted RSD
2.0 0.41 0.59 0.73 0.85
2.5 0.52 0.74 0.92 1.06
3.0 0.62 0.89 1.10 1.27
Unless otherwise prescribed, the maximum permitted RSD does not exceed the appropriate value given
in Table of repeatability requirements. This requirement does not apply to tests for related substance.

4. 𝐹𝑜𝑟𝑚𝑢𝑙𝑎
𝑡 𝑑𝑖𝑠𝑡𝑟𝑢𝑏𝑎𝑡𝑖𝑜𝑛 = 1 − α/2
Example
𝑡 𝑑𝑖𝑠𝑡𝑟𝑢𝑏𝑎𝑡𝑖𝑜𝑛 for 90% probability
level (double sided)
Step - 1:
100% – 90% = 10%
Step – 2:
α = 10/100 = 0.1
Step – 3:
𝑡 𝑑𝑖𝑠𝑡𝑟𝑢𝑏𝑎𝑡𝑖𝑜𝑛 = 1 −
0.1
2
= 0.95
How to calculate t distribution value for student t table using t table
How to calculate degrees of
freedom
Degrees of freedom (d.f.) = n−1
Example
For six replicate injection,
d.f = n-1 = 6-1 = 5

5. T.INV.2T function
Returns the two-tailed inverse of the Student's t-distribution.
Syntax
T.INV.2T(probability,deg_freedom)
The T.INV.2T function syntax has the following arguments:
•Probability Required. The probability associated with the Student's t-distribution.
•Deg_freedom Required. The number of degrees of freedom with which to characterize the distribution.
How to calculate probability
90% probability level (double sided)
Step - 1:
100% – 90% = 10%
Step – 2:
α = 10/100 = 0.1
How to calculate degrees of freedom
Degrees of freedom (d.f.) = n−1
Example
For six replicate injection,
d.f = n-1 = 6-1 = 5
How to calculate t distribution value for student t table using MS excel

6. Thanks