Purified Water Testing in Pharmaceuticals

Testing of Water Samples

• pH: -

1. Use pH meter previously calibrated using three point calibration method at pH
2. 4.0, pH 7.0 and pH 10.0 using NIST traceable standard buffers.
3. Calibration Frequency: Daily
4. Acceptance Criteria: Variance NMT 0.05
5. Always preserve the electrode in saturated Kcl solution.
6. Rinse clean the electrode with purified water
7. While testing ensure temperature probe is inserted in the solution.

• Conductivity: -

1. Use Conductivity meter calibrated using 5 microcemens and 10 microcemens conductivity standards traceable to NIST.
2. Calibration Frequency: Daily
3. Acceptance Criteria: Variance NMT 5%
4. Always preserve the electrode in purified water.
5. Rinse clean the electrode with purified water
6. While testing ensure temperature probe is inserted in the solution

• TOC ( Total Organic Carbon Test):

1. The test is based on the principles of Oxidative combustion of carbonaceous material at high temperature like 680 °C in presence of platinum catalyst.
2. Total Carbon = Total Organic Carbon + Inorganic carbon
3. During testing Inorganic carbon is removed by air sparging and the remaining carbon is measured as Total Organic carbon.
4. Daily Calibration: Linear curve using Blank run with zero water and 500 ppb Sucrose solution is carried out daily based on which the samples of the day will be tested.
5. System Suitability: 500 ppb Parabenzoquinone solution is tested and the comparison made with the linear curve obtained using Blank and 500 ppb sucrose. The % recovery of PBQ should be within 85-115 %
6. Oxidisable substances is only a qualitative method used as an optional method to TOC

• Heavy Metals:

0.1 ppm lead nitrate standard and sample tested parallely .after addition of acetate buffer and thioacetamide the intensity of color developed in sample should be not more intense than the standard.

• Nitrate: 

Water sample and 0.2 ppm nitrate standard tested parallaly by adding Kcl and diphenylamine solution. Dropwise H2SO4 addition develops a blue color which should be not more intense in sample compared to standard.

Tests for Potable Water

• Hardness : 

Total hardness, which is the sum of calcium and magnesium concentrations, both expressed as calcium carbonate, in milligrams per liter, is determined by EDTA titrimetric method

• Chlorides: 

Water sample treated with dil. Nitric acid and silver nitrate gives opalescence which should be less than one observed with 250 ppm chloride standard treated in the same manner.
• Test for total microbial count:
1. 1 ml of potable water sample directly plated and mixed with plate count agar and incubated at 30-35°C for 72 hrs. After incubation count the no. of cfu.
2. For purified water and WFI required qty is filtered through 0.45 micron membrane filter and filter is placed on plate count agar and incubated.

• Bacterial Endotoxins test:

Endotoxin in sample reacts with amebocyte cell lysate and forms a firm gel indicative of positive reaction.

• Test for Coliforms:

1. Indicates whether or not the water is potable I.e. can be consumed by human.
2. Indicates faecal contamination level and is a standrad for Drinking water quality.
3. Tested using a set of 15 MacConkeys Broth tubes. The tubes showing acid and gas production will be again inoculated in Mac.Broth for avoiding false positives.
4. From confirmed positives the no. of tubes showing Acid and gas production are compared with MacCrady’s table.