Testing Items and Related Supporting Reagents for Purified Water in the 2020 Chinese Pharmacopoeia

Purified water is commonly used in the pharmaceutical industry and holds a significant position. It is widely applied in multiple aspects such as the preparation, extraction, and cleaning of pharmaceutical formulations. China's "Good Manufacturing Practice for Pharmaceutical Products" (GMP) and related regulations impose strict requirements on pharmaceutical water, especially purified water. GMP emphasizes that pharmaceutical water should be suitable for its intended use and comply with the quality standards of the Chinese Pharmacopoeia. It requires that storage tanks and pipeline materials be non-toxic, corrosion-resistant, and prevent microbial growth. The Pharmacopoeia stipulates that purified water must be prepared by methods such as distillation or ion exchange, and its quality must meet specified standards. It can be used for the preparation and extraction of various formulations but must not be used for injections. The latest draft of the "0261 Pharmaceutical Water Standard" further emphasizes control over elemental impurities and microbial contamination to ensure the quality and safety of purified water during preparation, storage, and distribution. 

What are the testing items for purified water?
The 2020 edition of the Chinese Pharmacopoeia specifies 10 testing items for purified water: Appearance, Conductivity, Total Organic Carbon/Easily Oxidizable Substances, Microbial Limit, pH Value, Nitrate, Nitrite, Ammonia, Non-Volatile Residues, and Heavy Metals. Below are the functions of each testing item and introductions to related supporting reagents:

1. Appearance: Ensures that purified water is clear and transparent with no visible impurities.
   No specific reagents listed.
2. Acidity/Alkalinity (pH Value): Determines the acidity or alkalinity of water, originally using methyl red and bromothymol blue indicator solutions.
   • PCL-2021ZSY018: Methyl Red Indicator Solution, 0.5 mg/mL, 100 mL/bottle
   • PCL-2021ZSY058: Bromothymol Blue Indicator Solution, 0.5 mg/mL, 100 mL/bottle
     Note: Based on guidance from various pharmacopoeias and USP<1231> Chlorine-Ammonia Model, the Pharmacopoeia Commission has revised the acidity/alkalinity test. By using the conductivity measurement method for pharmaceutical water (General Chapter 0681), specifically the method for water for injection, the pH value naturally falls within 5.0–7.0 when conductivity meets standards. This range strictly covers the pH range of the original methyl red and bromothymol blue indicators. Therefore, the Pharmacopoeia Commission proposes eliminating the separate acidity/alkalinity test to simplify procedures and ensure water quality.
3. Nitrate: Determines the nitrate content in water, requiring the preparation of 10% potassium chloride solution, 0.1% diphenylamine sulfate solution, and standard nitrate solution.
   • PCL-2021RY003: Potassium Chloride Solution, 100 mg/mL, 100 mL/bottle
   • PCL-2021RY011: Diphenylamine Sulfate Solution, 0.10%, 100 mL/bottle
   • PCL-2021SY213: Nitrate-Free Water, /, 500 mL/bottle
   • PCL-2021BZ028: Standard Nitrate Solution, 1 μg/mL, 100 mL/bottle
     Note: For nitrate and nitrite testing, new methods adopt multi-stage conductivity testing (three-step method) to evaluate purified water quality more efficiently, reducing the complexity of inorganic ion chemical tests and ensuring purity and safety.
4. Nitrite: Determines the nitrite content in water.
   • PCL-2021RY010: Sulfanilamide Dilute Hydrochloric Acid Solution, 10 mg/mL, 250 mL/bottle
   • PCL-2021RY028: N-(1-Naphthyl)ethylenediamine Dihydrochloride Solution, 1 mg/mL, 250 mL/bottle
   • PCL-2021BZ048: Standard Nitrite Solution, 1 mg/mL, 100 mL/bottle
   • PCL-2021SY214: Nitrite-Free Water, /, 500 mL/bottle
5. Ammonia: Determines the ammonia content in water.
   • PCL-2021SY211: Alkaline Potassium Iodomercurate, /, 100 mL/bottle
   • PCL-2021SY125: Ammonium Chloride Test Solution, 31.5 mg/L, 100 mL/bottle
   • PCL-2021SY210: Ammonia-Free Water, /, 500 mL/bottle
     Note: The Pharmacopoeia Commission revised the ammonia test standard, setting a limit of 0.3 ppm (0.00003%) based on an ammonia model. When conductivity is ≤1.3 μS/cm at 25°C, ammonia concentration is controlled below 0.3 ppm, aligning with the first step of the water for injection conductivity method to ensure purity and safety.
6. Conductivity: Reflects ion concentration and conductivity in water; must comply with General Chapter 0681.
   • PCL-2021RY003: Potassium Chloride Solution, 100 mg/mL, 250 mL/bottle
   • PCL-2024DD523: Sodium Chloride Solution, 0.1 mol/L, 500 mL/bottle
   • PCL-2021SY227: Sodium Acetate Test Solution, Test Solution [2020Chp], 100 mL/bottle
7. Non-Volatile Residues: Determines the content of non-volatile substances by gravimetric measurement of residues after water evaporation, controlling non-volatile organic and inorganic compounds.
   No specific reagents listed.
8. Easily Oxidizable Substances: Determines the content of easily oxidizable substances.
   • PCL-2021SY133: Dilute Sulfuric Acid, 10%, 500 mL/bottle
   • PCL-2020DD048: Potassium Permanganate Titrant, 0.02 mol/L, 500 mL/bottle
9. Heavy Metals: Essential for heavy metal inspection. The European Pharmacopoeia requires elemental impurity risk assessment if conductivity is non-compliant. China primarily uses chemical precipitation to detect lead content; studies show that lead is controlled below 0.1 ppm when conductivity meets standards.
   • PCL-2020HC028: Acetate Buffer Solution, pH 3.5, 250 mL/bottle
   • PCL-2021SY105: Thioacetamide Test Solution, Solution A, 20 mL/bottle; Solution B, 100 mL/bottle
   • PCL-2021BZ018: Standard Lead Solution, 10 μg/mL, 100 mL/bottle
10. Microbial Limit: Microbial monitoring must follow requirements in General Chapter 0261 for pharmaceutical water.