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INTERVIEW QUESTIONS ON SYSTEM SUITABILITY PARAMETERS - HPLC & GC

1) WHAT IS SYSTEM SUITABILITY TEST? EXPLAIN SST PARAMETERS IN HPLC or GC?

The system suitability test is used to verify that the chromatographic system is suitable for the intended analysis or not. That is to ensure that the complete testing system including instruments, electronics, reagents, column & analyst is suitable for intended application.

The main system suitability parameters are
1. Precision
2. Capacity factor
3. Selectivity factor
4. Resolution
5. Theoretical plate count
6. Tailing factor
7. Signal to Noise ratio
8. Peak to valley ratio

2) WHAT IS PRECISION? EXPLAIN?

It is the closeness with which results of replicate analysis of a sample agree. Usually expressed in terms of %RSD.
%RSD = Standard Deviation*100/Mean.

For Assay by HPLC, the maximum permitted relative standard deviation does not exceed the appropriate value given in the below table as per USP & EP.



Note:

1.B (percent) means upper limit of your assay -100.
That is If your assay limit is 98%-102%, B (percent) is 102%-100% = 2.0
That implies your %RSD should not more than 0.85% for 6 injections and 0.73 for 5 injections.

2.This requirement does not apply to tests for related substances.

3) WHAT IS CAPACITY FACTOR or RETENTION FACTOR?
It is the ratio of the adjusted retention volume (or time) to the hold-up or Void volume (or time). (or) It is the migration rate of analyte on a column (or) It is a measure of time of sample component resides in the stationary phase relative to the time it resides in the mobile phase.

Simply it is measure of where the peak of interest located with respect to void volume (retention volume of unretained compound).

Capacity factor (K¹) = VR¹/Vm = tR¹/ tm = (tR-tm)/tm

VR¹= Retention volume of analyte.
VM=Retention volume of unretained compound
tR=Retention time of analyte.
tm or to=Retention time of unretained compound

Note:
1. Generally the ideal valve of K¹ is in between 2 to 5. But the acceptable valve is in between 1 to 20 .

4) WHAT IS SELECTIVITY FACTOR or RELATIVE RETENTION? EXPLAIN?
The relative retention of two peaks in a column is known as selectivity factor. It is the ratio of adjusted retention time of a compound to that of another used as reference obtained under identical conditions.

Selectivity factor (a ) = K2/K1 = (tR2-tm)/ (tR1-tm)

tR2=Retention time of our analyte
tR1=Retention time of reference compound.

Note:
1. As per USP the selectivity factor should be always greater than 1.

5) WHAT IS RESOLUTION? EXPLAIN?
Resolution is the ratio of distance of separation of band maxima to their average base width. (or) The distance between the peak centers of a two analyte peaks divided by the average base width of the peaks.

“It is the ability of a chromatographic column to separate peaks. It is usually expressed in terms of the separation between two adjacent peaks”

As per USP:


Resolution(R) = 2 (tR2-tR1)/ (w1+w2)

tR2&tR1 are retention times of two components.

w1&w2 are corresponding peak widths at base.

As per EP:

Resolution(R) = 1.18 (tR2-tR1)/ (wh1+wh2)

tR2&tR1 are retention times of two components

wh1&wh2 are corresponding peak widths at half height.

Note:
1. Base line resolution achieved at R=1.5. But more than two is desirable.
6) WHAT IS THEORITICAL PLATE? HOW NUMBER OF THEORITICAL PLATES EFFECT THE COLUMN EFFICIENCY? EXPLAIN?

Martine & Synge used a chromatographic model involving a hypothetical division of column in to no. of plates known as theoretical plate. So, Theoretical plate is an imaginary part of the column.

The theoretical plate number (N) is a measure of the efficiency per unit length of the column.

As per USP:


Number of theoretical plates (N) = 16 (tR/W) 2

tR=Retention time of analyte

W=Peak width at base

As per EP:

Number of theoretical plates (N) = 5.54 (tR/Wh) 2

tR=Retention time of analyte

Wh =Peak width at half height.

7) WHAT IS SYMMETRY FACTOR or TAILING FACTOR? EXPLAIN?

1. Theory assumes an ideal symmetric peak which is known as Gaussian peak. The front side deviation from the Gaussian peak is known as peak fronting & rear side deviation is known as peak tailing.

2. It is a factor which describing shape of a chromatographic peak. And it is a measure of peak tailing.

Define Tailing factor:

“the distance from the front slope of the peak to the back slope divided by twice the distance from the center line of the peak to the front slope, with all measurements made at 5% of the maximum peak height”.
As per USP & EP:

Tailing factor (As) = w 0.05/2d

w 0.05=Width of peak height at one-twentieth of peak height

d=Distance between the perpendicular dropped from the peak maxima and the leading edge of the peak at one-twentieth of the peak height

Note:
1. As per EP, In related substance test or assay the symmetry factor should be in between 0.8 to 1.5 unless otherwise specified prescribed.


8) WHAT IS SIGNAL TO NOISE (S/N) RATIO? EXPLAIN?

The short term noise influences the precision of quantification. So S/N ratio is a useful system suitability parameter to identify noise effect on quantification of impurities..etc.

Signal to noise(S/N) ratio is calculated from following equation


S/N = 2H/h

Where

H= Height of concerned peak measured from the peak apex to the base extrapolated over a distance ≥5 times the peak width at its half height.

h= Difference between the largest and smallest noise valves observed over a distance ≥5 times width at half height of the peak.




9) WHAT IS PEAK TO VALLEY (p/v) RATIO EXPLAIN?

Peak to valley (p/v) ratio may be employed as system suitability criterion in a test for related substance when baseline separation between two peaks is not achieved.

p/v = Hp/Hv Where

Hp= Height above the extrapolated baseline of the minor peak.
Hv= Height above the extrapolated baseline at the lowest point of the curve separating the minor and major peaks.


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