1.0 | 6122 LAB - Drug Monograph & USP

Pharmacopeia

- official compilation of monographs

- book of public standards for medicines, dosage forms, drug substances, excipients, biologicals, compounded preparations, medical devices, dietary supplements, and other therapeutics

Specification Sheet

- a detailed document containing different tests that a specific material must undergo

- gives a clear overview of the sample's conformity with the standards (ie. Pharmacopeia)

Pharmacopeia: Contents (6)

1. Drug monographs

2. Quality control standards

3. Analytical methods

4. Dosage forms

5. Packaging and labeling requirements

6. Storage conditions

USP number (USP 43) > NF number (NF 38)

since its first edition was released earlier

USP

- United States Pharmacopeia

- Uniform set of guidelines for best understood medicinal substances and preparations

- monographs of APIs or active ingredients

USP First Edition: Year

1820

NF

- National Formulary

- Standards for excipients, botanicals, and other similar products

- monographs of inert substances

NF First Edition: Year

1888

USP-NF Online: Official text

https://online.uspnf.com

USP-NF Online: Latest version

USP-NF 2025 Issue 2

- February 03, 2025

USP-NF Online: Revision

revised thrice yearly

Philippine Pharmacopeia

- published 2004

- inactive, no latest revisions

- due to its inactivity, the PH's primary source is USP

Major Pharmacopeias (4)

1. US Pharmacopeia

2. European Pharmacopeia

3. British Pharmacopeia

4. Japanese Pharmacopeia

Regional Pharmacopeias (3)

1. African Pharmacopeia

2. WHO International Pharmacopeia

3. European Pharmacopeia

Official Text

- Published in the USP-NF online

- Routine revisions are published online & become official six months after publication

Official Text: Discontinued (2)

1. Print version

2. USB flash drive version

Latest USP Print version

USP 43-NF 38

Latest USP USB version

USP 42-NF 37

Identifying Official Text (3)

1. Currently Official

2. Not Yet Official

3. No Longer / Never Official

Official Articles

- Article (drug substance/drug materials) recognized by USP-NF

- Monograph of the article is published in the compendium (pharmacopeia)

- Involves official substances (raw materials) & official products (finished products)

Acceptance Criteria

- Allow for analytical error, for unavoidable variations in manufacturing and compounding, and for deterioration to an extent considered acceptable under practical conditions

- a range of acceptance wherein an article will still be considered as in compliance with standards

- formulated with the intent to provide 100% of the quantity of each ingredient declared on the label

General Chapters (5)

1. Descriptions of tests and procedures for application

2. Descriptions and specifications of conditions and practices for pharmaceutical compounding

3. General information for the interpretation of the requirements

4. Descriptions of general pharmaceutical storage, dispensing, and packaging practices

5. General guidance to manufacturers of official substances or products.

< 1000

applicable to an article

1000 to 1999

informational purposes only

> 2000

applicable only for dietary ingredient & dietary supplements

Monograph

- Written document or standard that describes an item

- article's name, definition, specifications, and other requirements related to packaging, storage, and labeling

- ensure strength, quality, and purity of article

Item

- will become a commercially available finished product

- can be a drug product or ingredient, or a food chemical

Monograph: Specifications (3)

1. Tests

2. Procedures

3. Acceptance criteria

Monograph Components (8)

1. Molecular Formula

2. Added Substances

3. Description and Solubility

4. Identification

5. Assay

6. Impurities and Foreign Substances

7. Performance Tests

8. USP Reference Standards

Molecular Formula

- Define the required strength of a compendial article

- chemical entity or entities, as given in the complete chemical name of the article, having absolute purity

Added Substances

- Unsuitable for inclusion in an official article

- Not all monographs contain this component

- allowed if permitted by the monograph

Added Substances: AKA

Adulterants

Added Substances must not be listed if they (2)

1. impair the bioavailability, therapeutic efficacy or safety of the official article

2. interfere with the assays and tests prescribed for determining compliance with compendial standards

Added Substances in Official Substances

- Must not exceed the minimum quantity required for providing their intended effect

- Labels should indicate names and amounts of added substances

Added Substances in Official Products (3)

1. to enhance stability, usefulness, or elegance, or to facilitate its preparation

2. In compounded preparations

3. In dietary supplements

Description and Solubility

- General test

- Physical and chemical description

- Not a standard

- if a product's expected solubility is not met, it can be said adulterated or with impurities

Very soluble

To dissolve 1g: < 1

Freely soluble

To dissolve 1g: 1 - 10

Soluble

To dissolve 1g: 10 - 30

Sparingly soluble

To dissolve 1g: 30 - 100

Slightly soluble

To dissolve 1g: 100 - 1,000

Very slightly soluble

To dissolve 1g: 1,000 - 10,000

Practically insoluble

To dissolve 1g: > 10,000

Identification

- Aid in verifying the identity of articles as they purported to be

- Establish whether the sample is the article named in USP-NF

- May consist of one or more procedures

- ALL requirements must be met to satisfy the requirements of the tests

Identification: Arrangement

based on the chronological order of approval, not on importance

Assay

- Official test in the event of a question or dispute regarding the preparation's conformance to official standards

- performed when a product is recalled

Assay: Retention sample

- a portion taken from a raw material at different stages/every step

- kept aside for future reference

Impurities and Foreign Substances

- Provided to limit substances to amount unobjectionable under conditions in which article is customarily employed

Impurities and Foreign Substances: similar to

Added Substances, but this is more accepted

Impurities: after chromatography

No impurity shall be detected or present after chromatography

Impurities: Amount and identity of the impurity

shall be stated in the labeling or certificate of analysis of the official substance

Impurities: Unacceptable amount

The presence of any unlabeled other impurity in an official substance is unacceptable if 0.1% or greater from the standards.

Impurities: must not exceed _

Must not exceed 2.0% - sum of all other impurities combined

Impurities: Toxic substances

- Any known toxic substance shall not be listed

- have their own monograph called "Material Safety Data Sheet"

Performance Tests

- For drug products or finished products where content uniformity determinations have been made using the same analytical methodology specified in the Assay.

- In short, it checks the performance of the dosage form as a dosage form.

USP Reference Standards

- Authentic specimens that have been approved as suitable for use as comparison standards in USP/NF tests and assays

- used in accordance with the instructions on the label

results obtained using specified USP RS

Only results obtained using specified USP RS are conclusive

Test Results: Rounding Rules

- Calculated values should be rounded off to the number of decimal places that is in agreement with the limit expression

- dictated by # of decimal places in the acceptance criteria

Rounding Rules: Calculations

- Round off only in the final calculations

- Intermediate calculations may be rounded off for reporting purposes, but original value must be used for any additional required calculations

- Acceptance criteria are fixed numbers and are not rounded

RS

USP Reference Standard

CS

Colorimetric Solution

TS

Test Solution

VS

Volumetric Solution

"About"

A quantity within 10%

e.g., "About" 100 mg: you can use 90 - 100 mg

Alcohol Content

Percentage by volume of C2H5OH at 15.56°C

Alcohol vs. Dehydrated alcohol

A: ethyl alcohol or ethanol

DA: absolute alcohol or anhydrous alcohol

Alcohol in RS

Reference Standard will always be 100% ethanol

Blank Determinations

- same quantities

- of same reagents

- treated in the same manner as solution containing test substance but without the substance itself.

Desiccator

- Use of a tightly closed container of a suitable size and design

- maintains atmosphere of low moisture content by means of suitable desiccant

Desiccator: Examples (3)

1. Anhydrous Calcium Chloride

2. Silica Gel

3. Magnesium Perchlorate

Negligible

Quantity not exceeding 0.50 mg

Ex. If the sample is 50mg, the negligible weight is less than 0.50mg

Odor

- Evaluation of suitable quantity of freshly opened material

- after exposure to the air for 15 minutes

- Not a specific standard for purity

Odor: Descriptions (3)

1. Odorless

2. Practically odorless

3. With a faint characteristic of odor

Percent: % w/w

For mixtures of solids and semisolids

Percent: % w/v (2)

For solutions or suspension of solids in liquids

For solutions of gases in liquids

Percent: % v/v

For solutions of liquids in liquids

Percent Concentrations (3)

% w/w

% w/v

% v/v

Pressure

by use of suitable manometer or barometer

Specific Gravity

Weight of a substance in air at 25° divided by the weight of an equal volume of water at the same temperature

Temperature

- in degrees Celsius

- All measurements at 25°C , unless indicated

Temperature: Alcohol

If it is alcohol, 15.56°C

Water: Ingredient in an Official Product

meet requirements of appropriate water monograph

Water: Manufacture of Official Substances

meet requirements for drinking water

Water: Compendial Procedure

meet requirements for Purified Water USP

Weights & Measures

- International System of Units (SI)

- "weight" = "mass"

- degrees (°) without any qualifying unit of measure = degrees Celsius (°C)

Molality (m)

Moles solute / kg of solvent

Molarity (M)

Moles solute / L solution

Normality (N)

Equivalent solute / L. solution

Length (6)

m

cm

mm

μm/mcm

nm

Å

Mass (8)

kg

g

mg

μg/mcg

ng

pg

Da

kDa

Time (3)

s

min

h

Volume (4)

L

dL

mL

μL/mcL

Temperature (1)

℃

Amount of substance (7)

mol

mmol

μmol

Eq

mEq

Osmol

mOsmol

Pressure (4)

Pa

kPa

psi

mm Hg

Pharmacopeia: Importance (3)

1. give public standards for comparison of quality

2. give assurance of uniformity, consistency and quality of ingredients and products

3. control the quality of pharmaceutical, dietary supplements, and food ingredient products

Parts of Monograph (6)

1. Official Title

2. Molecular formula

3. Identification

4. Assay

5. Impurities

6. USP RS

2. Molecular formula

chemical names, structure, and definition

2. Molecular formula: Definition

includes the acceptance criteria for the assay portion

Identification

includes the acceptance criteria for the assay portion