How each QC test is actually done.
Search by analyte, sample type or technique. Every method shows the principle, preparation, instrument settings, system suitability and a worked calculation.
Finished products
Tablets, capsules, injections, oral liquids, creams.
Assay of Paracetamol Tablets by HPLC
HPLCDetermines how much paracetamol is present in a tablet compared with the label claim, using reversed-phase HPLC with UV detection at 243 nm and an external reference standard.
Open methodRelated Substances (Impurities) by HPLC
HPLCSeparates the drug from its process impurities and degradation products and reports each impurity as a percentage of the drug, using a diluted standard and relative response factors. Paracetamol tablets are used as the example, where the key degradation product is 4-aminophenol.
Open methodDissolution of Immediate-Release Tablets (Paracetamol 500 mg example)
Dissolution + UV / HPLCMeasures the percentage of paracetamol released from each of six tablets after 30 minutes in 900 mL of phosphate buffer at 37 °C, stirred by a paddle at 50 rpm, and judges the batch against the Q value using the staged acceptance criteria.
Open methodUniformity of dosage units
HPLC / UVChecks that each individual tablet or capsule contains close to the labelled amount of drug. Ten units are tested and the result is expressed as an acceptance value (AV) that combines how far the mean is from target and how spread out the units are.
Open methodDisintegration Time of Tablets and Capsules
Disintegration testerChecks that six dosage units break up completely within a stated time when moved up and down in fluid at 37 °C.
Open methodTablet Hardness (Breaking Force) and Friability
Physical testingMeasures the force needed to break individual tablets and the percentage of weight lost when a sample of tablets is tumbled for 100 revolutions.
Open methodAverage Weight & Weight Variation of Tablets
BalanceWeighs 20 tablets individually, calculates the average weight, and checks how far each tablet deviates from the average against the limit for that tablet size.
Open methodParticulate Matter in Injections by Light Obscuration
Light obscurationCounts sub-visible particles of 10 µm and above and 25 µm and above in an injection using a light obscuration counter, and compares the counts per container (or per mL) with pharmacopoeial limits.
Open methodpH of a Solution (Finished Products)
pH meterMeasures the pH of a liquid product, or of a solution of a solid product prepared as the monograph describes, using a pH meter calibrated with buffers that bracket the expected pH.
Open methodOsmolality of Parenterals (Freezing-Point Depression)
OsmometerA small, exact volume of the product is supercooled and frozen in a calibrated freezing-point osmometer. The instrument measures the freezing point depression and reports osmolality in mOsm/kg.
Open methodViscosity of Oral Liquids (Rotational Viscometer)
ViscometerThe sample is brought to a controlled temperature and its viscosity is measured with a rotational viscometer using the spindle and speed given in the STP, with the reading taken at a fixed time and within the reliable torque range.
Open method
APIs & raw materials
Active ingredients and excipients on receipt.
Identification by FTIR
FTIRConfirms the identity of a raw material by recording its infrared spectrum and showing that it matches the spectrum of the reference substance (or the official reference spectrum) measured the same way.
Open methodIdentification by UV
UV-VisSupports the identity of a raw material by showing that its UV spectrum has absorption maxima (and minima) at the expected wavelengths and that its absorbance at the maximum agrees with the reference substance or with the stated specific absorbance.
Open methodWater Content by Karl Fischer Titration (Volumetric)
KF titrationDetermines the percentage of water in a raw material by dissolving a weighed sample in dry methanol and titrating with a standardised Karl Fischer reagent to an electrometric endpoint.
Open methodLoss on Drying (Oven Method)
Oven / moisture analyserMeasures the percentage of mass a sample loses when dried under stated conditions, commonly at 105 °C to constant weight. The loss includes water and any other volatile matter.
Open methodResidual Solvents by Headspace GC-FID
GC headspaceMeasures leftover organic solvents from synthesis or purification in an API or excipient. The sample is dissolved in DMSO in a sealed headspace vial, heated, and the vapour is injected into a GC-FID. Each solvent is quantified against a standard prepared at its ICH Q3C limit.
Open methodElemental Impurities by ICP-MS
ICP-MSMeasures trace levels of toxic elements in an API after dissolving it completely by closed-vessel microwave digestion. Results are compared with permitted concentrations derived from ICH Q3D permitted daily exposures (PDEs) and the control threshold.
Open methodSulphated Ash / Residue on Ignition
Muffle furnaceMeasures the inorganic impurities left after an organic substance is charred with sulphuric acid and ignited at 600 ± 50 °C to constant mass. The residue is reported as a percentage of the sample.
Open methodSpecific Optical Rotation (Raw Materials)
PolarimeterA solution of the substance is prepared at the concentration stated in the monograph, its optical rotation is measured in a polarimeter at 589 nm and the stated temperature, and the specific optical rotation is calculated on the dried (or anhydrous) basis.
Open methodMelting Range by the Capillary Method (Paracetamol, illustrative)
Melting point apparatusMeasures the temperature range over which a finely powdered, dried sample packed in a capillary melts when heated slowly. Used as an identity and purity test for crystalline raw materials.
Open methodAssay of an Acidic API by Potentiometric Titration (Ibuprofen, illustrative)
TitrationDetermines the purity of an acidic API, here ibuprofen, by dissolving it in methanol and titrating the carboxylic acid group with standardised 0.1 M sodium hydroxide, locating the equivalence point potentiometrically.
Open methodLimit Tests for Chloride & Sulphate
Wet chemistryA semi-quantitative check that a raw material does not contain more chloride or sulphate than a set limit. The sample solution is treated with silver nitrate (chloride) or barium chloride (sulphate), and the opalescence formed is compared with that of a standard containing a known amount of the ion.
Open methodParticle Size Distribution by Laser Diffraction
Laser diffractionMeasures the volume-based size distribution of a powder by laser diffraction and reports D10, D50, D90 and span against the specification.
Open methodBulk and Tapped Density of Powders
Tap density testerMeasures how much space a weighed powder takes up before and after mechanical tapping, and calculates bulk density, tapped density, Carr's index and Hausner ratio as indicators of flow.
Open method
Pharmaceutical water
Purified water, WFI and potable water.
Conductivity of Purified Water
Conductivity meterTests purified water for ionic contamination using the three-stage USP <645> approach: a temperature-dependent limit at Stage 1, a stirred CO₂-equilibrated test at Stage 2, and a pH-dependent limit at Stage 3.
Open methodTotal Organic Carbon (TOC) in Purified Water
TOC analyserTests purified water for organic contamination by oxidising organic compounds to CO₂ and measuring it. The sample response is compared with the limit response from a 0.50 mg/L carbon sucrose standard, after a system suitability test with 1,4-benzoquinone.
Open methodMicrobial Count of Pharmaceutical Water by Membrane Filtration
Membrane filtrationFilters a measured volume of water through a 0.45 µm membrane, places the membrane on R2A agar and counts colonies after incubation, giving cfu per mL (purified water) or cfu per 100 mL (WFI). Results are compared with alert and action levels and trended.
Open method
Microbiology
Microbial limits, sterility, endotoxins, environment.
Microbial Enumeration Test (TAMC / TYMC) by Plate Count
Plate countCounts the number of aerobic bacteria and fungi (TAMC) and of yeasts and moulds (TYMC) in a non-sterile product, by plating a 1:10 dilution of the sample onto Soybean-Casein Digest Agar and Sabouraud Dextrose Agar and counting colonies after incubation.
Open methodTests for Specified Microorganisms in Non-Sterile Products
Selective mediaShows whether named objectionable organisms are absent from a stated amount of product (usually 1 g or 1 mL), by enriching the sample in broth, sub-culturing onto selective and differential agars, and checking any suspect colonies with identification tests.
Open methodSterility Test by Membrane Filtration or Direct Inoculation
Membrane filtrationTests a sample of containers from a batch for the presence of viable microorganisms by filtering the product and incubating the membrane, or by placing the product directly into culture media, in Fluid Thioglycollate Medium and Soybean-Casein Digest Medium for 14 days.
Open methodBacterial Endotoxins Test (LAL) by Kinetic Chromogenic Method
Kinetic chromogenicMeasures endotoxin in a product by mixing a diluted sample with Limulus amebocyte lysate and a chromogenic substrate, reading the colour development at 405 nm and 37 °C, and converting the onset time to EU/mL using a log-log standard curve. Spiked samples show the product does not interfere.
Open methodEnvironmental Monitoring of Clean Areas (Viable)
Settle / contact platesMeasures the number of viable microorganisms in the air and on surfaces and personnel in clean areas, using settle plates, contact plates and active air samplers, and compares the counts with alert and action limits for each cleanroom grade.
Open methodGrowth Promotion Test of Culture Media
Culture mediaChecks that each batch of culture medium can support the growth of a small number (not more than 100 cfu) of specified reference organisms, by comparing recovery on the new batch with a previously approved batch.
Open method
In-process & stability
Blend uniformity, in-process checks, stability samples.
Blend uniformity
HPLC / UVChecks that the active ingredient is evenly mixed through a powder blend before compression or encapsulation, by sampling the blender at about 10 locations and assaying each sample.
Open methodStability-Indicating Assay by HPLC
HPLCAn assay method that is proven to measure the active ingredient accurately even when degradation products are present. It is demonstrated by forced degradation (acid, base, oxidation, heat, light), peak purity and mass balance, and then used to test stability samples.
Open method
Packaging materials
Primary and secondary packaging tests.
Container Closure Integrity (Leak Test) by Vacuum Decay and Dye Ingress
Vacuum decayChecks that a sealed container has no leak large enough to risk the product. Vacuum decay measures the pressure rise around a container in an evacuated chamber; dye ingress shows leaks by the entry of coloured dye under vacuum.
Open methodHydrolytic Resistance of Glass Containers (Surface Glass Test)
TitrationMeasures how much alkali the inner surface of a glass container releases into water under autoclave conditions. The containers are filled with water, autoclaved at 121 °C, and the water is titrated with 0.01 M hydrochloric acid. The result classifies the container and confirms it meets its glass type.
Open method