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Writing SOPs for preparation of various solutions

Procedures for preparation of various solutions are a very common task described in production and laboratory Standard Operating Procedures (SOPs).  To help you with this process below we gathered procedures for preparation of several frequently-used solutions:

  • Diluting Concentrated Acids to 1 molar (1M) solutions
  • Indicators
  • Standard Buffer Solutions (According to USP 27)
  • Special Solutions and Reagents

1. Diluting Concentrated Acids to 1 molar (1M) solutions

1.1. General Safety Notes. Wear gloves and protect the eyes with safety goggles or even better, a face shield. Dilution of concentrated acid should always be done in a fume cupboard. Add concentrated acid to water slowly. Never add water to a concentrated acid.
1.2. Hydrochloric acid: 36% HCl → 1M HCl. Add 83.5 mL of 36% hydrochloric acid to about 600 mL of distilled water in a 1 litre measuring cylinder and make up to 1L. 32% HCl → 1M HCl. As above, except use 96 mL of 32% hydrochloric acid.
1.3. Nitric Acid: 70% HNO3 → 1M HNO3. Add 62 mL of 70% nitric acid to about 700 mL of distilled water in a 1 litre measuring cylinder and make up to 1 L.
1.4. Sulfuric acid: 98% H2SO4 → 1M H2SO4. Add 54 mL of 98% concentrated sulfuric acid to about 700 mL of distilled iced water in a 1 litre measuring cylinder and make up to 1 L.
1.5. Acetic acid: 99.5% CH3COOH (Glacial acetic acid) → 1M CH3COOH. Add 57 mL of the Glacial acetic acid to about 600 mL of distilled water in a 1 litre measuring cylinder and make up to 1 L. Glacial acetic acid to about 600 mL of distilled water in a 1 litre measuring cylinder and make up to 1 L.

2. pH Indicators

Indicators are substances which change from one color to another when the hydrogen ion concentration reaches a certain value, different for each indicator (1), and used to determine the specified end-point in a chemical reaction or to indicate that a desired change in pH has been effected (2).
2.1. Litmus: Digest 25g of litmus powder with three successive, 100-mL portions of boiling alcohol, continuing each extraction for about 1 hour. Filter, wash with alcohol, and discard the alcohol filtrate. Macerate the residue with about 25 mL of cold water for 4 hours, filter, and discard the filtrate. Digest the residue with 125 mL of boiling water for 1 hour, cool, and filter (2).
2.2. Methyl orange: Dissolve 1g of methyl orange in 1 liter of water. Filter if necessary (1).
2.3. Methyl red: Dissolve 100 mg of methyl red in 100mL of 95% ethyl alcohol. Filter if necessary (2).
2.4. Phenolphthalein: Dissolve 1g of phenolphthalein in 100mL of 95% ethyl alcohol (2).



3. Standard Buffer Solutions (According to USP 27)

3.1. Components for Standard Buffer Solutions preparation

3.1.1. Potassium Biphthalate, 0.2 M. Dissolve 40.85g of Potassium Biphthalate [KHC6H4(COO) 2] in water, and dilute with water to 1000 mL.

3.1.2. Potassium Phosphate, Monobasic, 0.2 M. Dissolve 27.22g of Monobasic Potassium Phosphate (KH2PO4) in water, and dilute with water to 1000 mL.

3.1.3. Boric Acid + Potassium Chloride, 0.2 M. Dissolve 12.37g of Boric Acid (H3BO3) and 14.91g of Potassium Chloride (KCl) in water, and dilute with water to 1000 mL.

3.1.4. Potassium Chloride, 0.2 M. Dissolve 14.91g of Potassium Chloride (KCl) in water, and dilute with water to 1000 mL.

3.1.5. Carbon dioxide-free water is distillated water that has been boiled vigorously for not less 5 minutes and allowed to cool without contact with atmosphere.

3.2. Composition of Standard Buffer Solutions (for volume 200 mL). Place 50mL of solution 1 in a 200-mL volumetric flask, add the specified volume of the Solution 2 and add carbon dioxide-free water to volume 200 mL.


4. Special Solutions and Reagents

4.1. Bang’s reagent (for glucose estimation). Dissolve 100 g of K2CO3, 66 g of KCl and 160 g of KHCO3 in the order given in about 700 mL of water at 30ºC. Add 4.4 g of of CuSO4 and dilute to 1 liter after the CO2 is evolved. This solution should be shaken only in such a manner as not allow entry of air. After 24 hours 300 mL are diluted to 1 liter with saturated KCl solution, shaken gently and used after 24 hours; 50 mL equivalent to 10 mg glucose (1).

4.2. Biuret Reagent. Dissolve 1.5 g of cupric sulfat and 6.0g of potassium sodium tartrate in 500 mL of water in a 1000-mL volumetric flask. Add 300 mL of carbonate-free sodium hydroxide solution (1 in 10), dilute with carbonate-free sodium hydroxide solution (1 in 10) to 1000mL and mix (2).

4.3. Bromine Water. Prepare a saturated solution of bromine by agitating 2-3 mL of bromine with 100 mL of cold water in a glass-stoppered bottle (2).

4.4. Chlorine Water. Prepare a saturated solution of chlorine in water (2).

4.5. Denigè’s Reagent. Mix 5 g of yellow mercuric oxide with 40 mL of water, and while stirring slowly add 20 mL of sulfuric acid, then add another 40 mL of water, and stir until completely dissolved (2).

4.6. Lime water. Saturated solution of calcium hydroxide – 1.5 g of Ca (OH) 2 in 1000 mL of water . Use some excess, filter off CaCO3 and protect from CO2 of the air (1).

4.7. Mayer’s Reagent. Dissolve 1.358 g of mercuric chloride in 60 mL of water. Dissolve 5 g of potassium iodide in 10 mL of water. Mix the two solutions, and dilute with water to 100 mL (2).

4.8. Nessler’s Reagent. Dissolve 143 g of sodium hydroxide in 700 mL of water. Dissolve 50 g of red mercuric iodide and 40 g of potassium iodide in 200 mL of water. Pour the iodide solution into hydroxide solution, and dilute with water to 1000 mL. Allow the settle, and use the clear supernatant (2).

4.9. Pasteur’s salt solution. To 1000 mL of distilled water add 2.5 g of potassium phosphate and o.25 g of calcium phosphate(1).

4.10. Saline. Dissolve 9.0 g of sodium chloride in water to make 1000 mL (1).

1. CRC Handbook of Chemistry and Physics. 63rd edition. Editor: R.C.Weast. CRC Press.
2. U.S. Pharmacopeia. USP 27 / NF 22.

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Safety SOPs and validations

All organizations must have Safety SOP and/or instructions and many organizations conduct validations of new apparatus, processes and methods, including, in tenders. In practice however, not enough attention is given to the observance of safety rules during the validation and accordingly, these issues are not addressed properly during the preparation of a validation protocol. Unfortunately, it is very common to see the following phrase under the Safety section of the validation protocol: Execution of works should be conducted in accordance with applicable organization Safety SOP and/or instructions (which usually do not say anything about validation). This is a typical example of a formal and an unacceptable approach to safety issues.

There are 4 main reasons why there must be special attention to safety issues during validations of new apparatus, processes and methods:

  1. There is use of new, unfamiliar materials and methods.
  2. The validation work is regarded as a temporary, one-time job.
  3. A desire by the administration (and the employee) to complete the validation as soon as possible which is often conducted as additional (or even unpaid) work.
  4. No appropriate financial and engineering support for safety, especially when it requires significant costs.

The best way to mitigate these issues, it is necessary to include in the Safety SOP a section called “Safety validation of new equipment, processes and techniques“, where you can focus on the following provisions:

  1. In preparation for the validation, the safety protocol should be extensively elaborated, as it often deals with unfamiliar machines, materials and methods of work.
  2. The main sources of information about safety in the preparation of validation protocols are sections Safety, Warning and Precautions in manufacturer’s operating instructions, Material Safety Data Sheets (MSDS), and appropriate regulatory documents.
  3. During the preparation of the validation, take your time to identify the risks and provide safety measures with regard to the use of harmful chemicals, biological materials, mechanical injuries and danger of electric shock.
  4. The validation protocol should include a strategy for managing possible ecotoxical effects and waste treatment methods.
  5. If the MSDS states an emergency telephone number of the manufacturer for use in the event of a spill, fire or hazardous exposure, it should be noted in the validation protocol.
  6. Only trained and experienced individuals should be involved in carrying out the validation. All participants must pass safety training before the initiation of the validation.
  7. The commencement of the validation process should be approved by a safety officer.
  8. Based on the results of the validation, the report should identify the factors and actions that require special attention in terms of safety and these should be reflected in the relevant sections of future work instructions and SOPs.

Example: Temporary electrical connections that do not meet safety requirements, commonly used in the preparation of the new equipment for validation.


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5 Best Guides for Developing SOPs

Anyone who ever tried to rewrite or develop their own SOPs has encountered the difficlty of organizing and formatting the documents so that they will be in complience with tha latest requirments of the regulatory agencies. While we offer updated and editable SOPs, here we assembled a list of books that can serve as guidance for those who are interested in developing their own SOPs.

Number 1. Effective SOPs: Make Your Standard Operating Procedures Help Your Business Become More Productive (The Business Productivity Series Book 6)



This easy-to-read book will provide you with basic information on the common principles of generating effective SOPs. The impact of the book would have been stronger had it elaborated more on the use of graphics and symbols.

Included in this book

  • A refresher on how SOPs can benefit your business
  • The idea of writing pairs to write more effective SOPs
  • Creating a ‘SOP map’ to better use SOPs in an ongoing way
  • Linking your daily routines to your SOPs
  • 5 downloadable templates that you can use immediately


Number 2. How to Write Policies, Procedures & Task Outlines: Sending Clear Signals in Written Directions 3rd Edition


The most prominent feature of this guide is a set of guidelines that clearly explain the differences between policies, procedures and task lists. The book is written in easy-to-understand language without being overly simplistic and provides a step by step way to put together a complete manual from start to finish.  Using this guide, the reader should be able to create documents that that are easy for the user to follow and for the management to evaluate. The book provides plenty real-world examples that, in spite of coming from different industries, can be applied to any organization.

Number 3. Establishing a System of Policies and Procedures: Basic primer for writing effective policies and procedures quickly (kindle)


This book is probably the most popular in its category, partially because it is endorsed by the American Society for Quality. The book covers the basics of research, policies and procedure writing and is intended for anyone who is in charge of writing policies and procedures or work instructions. One prominent feature of the book is the 8-section writing format for policy and procedures documents. A Word-based complete template is emailed with the purchase of 1 or more PDF books. There are some typos found in the book, but they do not make the material less clear.

That being said if you are an experienced policy writer you may find this book a bit to basic and get more value from another book by the same author “Achieving 100% Compliance of Policies and Procedures”. Includes samples table of contents pages and sample policy and procedure documents and Word-based templates


Number 4. 7 Steps to Better Written Policies and Procedures: Instructional Guide to Filling in Writing Format Template 




This book is the elaboration of Chapter 4 in “Establishing a System of Policies and Procedures.” Among many similar books on policy and procedures writing, this one is probably one of the most straightforward.  The main idea here is the suggestion of the 7-step structure that if followed should allow developing clear and functional procedures. As such this book is probably more suited for individuals who are only beginning their procedures writing mission, and more advanced writers may find this book a bit simplistic. The book brings up and explains several technical points such as concise formatting, style, content, etc. followed by examples.  Some examples point out what styles and formats are inappropriate for use in procedures.

In terms of style and readability, this book may have been a bit shorter since some explanation and points are repetitive the author also spends a lot of time on conveying the importance of well written policies and procedures and thus this book seem to be more suited for novices in procedure writing. The actual explanation of the seven sections does not begin until Chapter 4.


Number 5. Achieving 100% Compliance of Policies and Procedures: Policy and Procedure Streamlining Tools and Processes




Writing effective policies and procedures is incomplete without an effective implementation and compliance assurance strategy. This book is an excellent resource for experienced writers as it deals not so much with actual procedures writing but rather with the challenges of implementation and compliance. The main strength of this book is the continuous improvement approach and the ideas of how to communicate new ideas to the rest of the businesses staff. Importantly it provides ways to assess and validate the effects of implementing certain policies and procedures.

The book provides a chapter on creating a communication control plan, which is key to ensuring your policies and procedures, are up-to-date and relevant to your organization. Another chapter provides guidance on establishing a compliance plan (including ways to perform measurements and validation).

A real-life case study is used to demonstrate the use and the effect of principles described in the book. The case-study leads the reader from a labor extensive process to a new method resulting in savings of millions of dollars. The book does not however provide good assessment on the cost of developing the procedures themselves.