USP general chapter <921> defines the procedure for water determination. The test preparation as per general chapter is as below;
Test Preparation— Unless otherwise specified in the individual monograph, use an accurately weighed or measured amount of the specimen under test estimated to contain 2 to 250 mg of water. The amount of water depends on the water equivalency factor of the Reagent and on the method of endpoint determination. In most cases, the minimum amount of specimen, in mg, can be estimated using the formula:
FCV / KF
in which F is the water equivalency factor of the Reagent, in mg per mL; C is the used volume, in percent, of the capacity of the buret; V is the buret volume, in mL; and KF is the limit or reasonable expected water content in the sample, in percent. C is between 30% and 100% for manual titration, and between 10% and 100% for the instrumental method endpoint determination.
Let us understand how to derive minimum sample weight using above procedure in case of instrumental method and manual titration.
A. Minimum sample weight for instrumental method:
Let us understand how to derive sample weight using above procedure in case of instrumental method. To further explain it, let me take an example of an API with below assumptions.
1. Water equivalency factor of KF reagent (popularly known as KF Factor) is 5mg/ml (F)
2. Consider 10% as the used volume in %, of the capacity of the burette (C)
Note: 10% is considered as recommended in general chapter <921> if measurement is done by using instrumental method
3. The KF instrument with the burette capacity of 10ml is available in a laboratory (V)
4. Specification for water content is NMT 0.5% (KF)
5. Reasonable water content in API is about 0.2% (KF)
Note: The reasonable water content can be understood from trend data or product development data or from stability data.
The amount of specimen (W), in mg, by considering value for ‘C’ as the specification of water content, can be calculated as below
5 x 10 x 10
W = ------------------------
0.5
= 1000 mg
The amount of specimen (W), in mg, by considering value for ‘C’ as the reasonable water content, can be calculated as below.
5 x 10 x 10
W = ------------------------
0.2
= 2500 mg
B. Minimum sample weight for manual titration:
Similarly, let us understand how to derive sample weight using above procedure in case of manual titration. To further explain it, let me take same example as given above, except below assumption for “C”.
1. Consider 30% as the used volume in %, of the capacity of the burette (C)
Note: 30% is considered as recommended in general chapter <921> if measurement is done
by manual titration
The amount of specimen (W), in mg, by considering value for ‘C’ as the specification of water content, can be calculated as below
5 x 30 x 10
W = ------------------------
0.5
= 3000 mg
The amount of specimen (W), in mg, can be calculated by considering value for “C” as the reasonable water content as below.
5 x 30 x 10
W = ------------------------
0.2
= 7500 mg
The approach of calculating sample weight by considering ‘reasonable water content’ can be a good idea as it reflects practical scenario. It can also be understood that sample consumption is three times more in case of manual titration. And hence determination of water content by KF using instrumental method is always advisable.
Determination of sample weight with 100% burette capacity is not considered as it does not provide worst case scenario and hence may not be necessary.
I hope you must have got an overview on selecting sample weight during water determination. Let me know how do you define sample weight for water determination and which approach do you follow during defining it?
Comments
Post a Comment