QAQC of Radiopharmaceuticals

RADIONUCLIDIC PURITY

This refers to the fraction of the total radioactivity that is attributable to the desired radionuclide, compared to any impurities from other intended radionuclides

Gamma spectroscopy

Test methods for radionuclidic purity

99.5

Radionuclidic purity acceptance criteria:, typically greater than ____% purity for diagnostic agents).

0.15

Radionuclidic purity acceptance criteria:, Depending on the radionuclide, specific limits for Radionuclidic contaminants are set (e.g., Mo-99 contamination in Tc-99m generators should be less than _____ µCi of Mo-99 per mCi of Tc-99m).

GAMMA SPECTROSCOPY

studies the energy spectra of gamma-ray sources, such as in the nuclear industry, geochemical investigation, and astrophysics. Spectroscopes, or spectrometers, are sophisticated devices designed to measure the spectral power distribution of a source.

RADIOCHEMICAL PURITY

This is the proportion of the total radioactivity that exists in the desired chemical form of the radiopharmaceutical, as opposed to other chemical forms (e.g., free radioisotope or byproducts)

• Thin-layer chromatography (TLC)

• High-performance liquid chromatography (HPLC)

• Electrophoresis

RADIOCHEMICAL PURITY Test methods

THIN LAYER CHROMATOGRAPHY

• involves placing a drop of the radiopharmaceutical on a strip and allowing a solvent to carry the compound across the strip.

• Is a method for analyzing mixtures by separating the compounds in the mixture.

• can be used to help determine the number of components in a mixture, the identity of compounds, and the purity of a compound.

HIGH-PERFORMANCE LIQUID CHROMATOGRAPHY

• separates the radiopharmaceutical based on its interaction with the column matrix and solvent, providing a detailed analysis of chemical forms

• Instead of a solvent being allowed to drip through a column under gravity, it is forced through under high pressures of up to 400 atmospheres.

ELECTROPHORESIS

• separates charged radiopharmaceutical components based on their migration in an electric field.

• Technique commonly used in laboratories to separate charged molecules like DNA, RNA and proteins according to their size.

• By comparing the bands of the DNA samples with those from the DNA marker, you can work out the approximate length of the DNA fragments in the samples

CHEMICAL PURITY

Refers to the absence of non-radioactive contaminants or chemical impurities in the formulation

Chemical impurities

can introduce toxicity, reduce the efficacy of the radiopharmaceutical, or interfere with the stability of the radioactive component.

• HPLC

• Atomic absorption spectroscopy (AAS)

• Mass spectrometry (MS)

• Inductively Coupled Plasma Mass Spectrometry (ICP-MS)

• Gas Chromatography (GC)

Chemical purity test methods

95

Chemical purity: Acceptance Criteria should be very high, usually above __%, to ensure the correct chemical species is being administered

ATOMIC ABSORPTION SPECTROSCOPY

• analytical technique used to determine how much of certain elements are in a sample.

• It uses the principle that atoms (and ions) can absorb light at a specific, unique wavelength. 

INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY

An analytical technique used to determine the concentrations of elements and their isotopes by ionizing elements in the samples with extremely high-temperature Argon (Ar) plasma and then using a mass spectrometer to measure the number of ions based on their mass-to-charge ratio (m/z).

GAS CHROMATOGRAPHY

• The sample solution injected into the instrument enters a gas stream which transports the sample into a separation tube known as the "column." (Helium or nitrogen is used as the so-called carrier gas.) The various components are separated inside the column.

• The detector measures the quantity of the components that exit the column. To measure a sample with an unknown concentration, a standard sample with a known concentration is injected into the instrument.

• The standard sample peak retention time (appearance time) and area are compared to the test sample to calculate the concentration.

Sterility

Ensures that the radiopharmaceutical is free of viable microorganism, as these compounds are often administered intravenously, directly into the bloodstream.

14

Sterility test method: This involves incubating samples of the radiopharmaceutical in growth media under specific conditions (aerobic and anaerobic) for ____ days to detect microbial growth.

Complete sterility

Sterility acceptance criteria: ______________ is required for all injectable products.

pyrogens

are fever-inducing substances, typically bacterial endotoxins that must be absent in radiopharmaceuticals to prevent adverse reactions in patients

• Limulus Amebocyte Lysate (LAL) test

• Rabbit pyrogen test

Pyrogen testing methods

Limulus Amebocyte Lysate (LAL) test

This is the most common pyrogen testing method and involves using blood cells from the horseshoe crab, which coagulate in the presence of bacterial endotoxins.

RABBIT PYROGEN TESTING

Involves injecting the sample into rabbits and monitoring their body temperature to detect pyrogenic activity.

175 EU per dose

Pyrogen testing acceptance criteria: Radiopharmaceuticals must comply with endotoxin limits, typically expressed in endotoxin units (EU). For example, injections should contain no more than _____________

pH

The ___ measures the acidity or alkalinity of the radiopharmaceutical formulation

7.0 ± 0.5

The pH must fall within specified limits, generally around physiological pH _______

Isotonicity

ensures that osmotic pressure of the radiopharmaceutical matches that of human blood (approximately 290 mosm/L)

hypertonic or hypotonic

A _________________ solution can cause pain, swelling, or damage at the injection site due to the movement of water across cell membranes.

HALF-LIFE VERIFICATION

This is the verification that the radioactive decay follows the expected half-life for the radionuclide being used.

Particle size

___________ determines where the radiopharmaceutical will localize in the body. For example, larger particles may be trapped in the lungs, while smaller particles may circulate in the bloodstream.

DYNAMIC LIGHT SCATTERING

measures particle size by analyzing the scattering of laser light by particles in suspension.

SPECIFIC ACTIVITY

This is the amount of radioactivity per unit mass of the radiopharmaceutical compound

VISUAL INSPECTION

ensures that the solution is clear, colorless, and free from particulates or other visible defects

STABILITY TESTING

ensures that the radiopharmaceutical remains physically, chemically, and radiologically stable over time under specified storage conditions

• Air sampling

• Surface swabbing

ENVIRONMENTAL MONITORING TEST METHOD

Air sampling

Monitoring for microbial contamination and particulates.

Surface swabbing

Ensures surfaces are free from microbial or particulate contamination.