Layout 4 - Butterworth Labs



Layout 4 - Butterworth Labs
New Enquiries, Client Visits, Contracts & Agreements
John A S Welch CChem MRSC MRQA
Head of Business Development
[email protected]
Quality Control Analysis
David A Riches BSc CChem MRSC
Head of Analytical Operations
[email protected]
BLP05 - Melamine Analysis
Projects, Method Development, Validation, Stability
and Non-Routine Analysis
David Bell BSc
Head of Projects
[email protected]
Quality Audits & Regulatory Issues
David J Hawkins BSc CBiol MIBiol MRQA
Head of Quality Assurance & IT
[email protected]
54-56 Waldegrave Road, Teddington, Middlesex TW11 8NY
Telephone: +44 (0) 20 8977 0750 Fax: +44 (0) 20 8943 2624
Email: [email protected] Website:
Designed by: Delaney Goss Ltd 01372 466 666
Melamine Analysis
In August 2009 the FDA issued its Guidance
to Industry on preventing melamine
contamination in pharmaceutical and food
products, due to economically motivated
Butterworth has verified the FDA’s CG-MS
screening method for the Presence of
Melamine, Ammeline, Ammelide, and
Cyanuric Acid.
Although Melamine has low toxicity, it is
believed that it and related compounds will
form insoluble crystals in urine, causing
kidney stones and renal failure.
The FDA considers ingredients or raw
materials to be “at-risk components” that
rely on a test for nitrogen content for their
identity, purity, or strength and that contain
nitrogen in amounts greater than 2.5%.
Some examples of “at-risk materials”
include those excipients which rely on the
USP <461> Nitrogen test:
- Albumin
- Ammonium salts
- Copovidone
- Crospovidone
- Gelatin
- Lactose
- Povidone
- Povidone-Iodine
The method for the determination of
Melamine requires a reporting limit of
<2.5ug/g therefore Mass spectrometry is
To overcome these issues Butterworth can
make use of a Chemiluminescence analyser
to determine Nitrogen content. With the
increased sensitivity of this type of analyser,
sample sizes can be kept to milligram
quantities and there is no requirement for
the use of strong acids.
the primary method to be used to qualify
and quantify it and related compounds.
Mass-spectrum data for melamine (tri-TMS)
Butterworh currently has developed
methods for Povidone and Lactose to confirm
absence of Melamine contamination.
Samples are extracted and the target
analytes are converted to the trimethylsilyl
derivative for analysis by CG-MS-MS.
14.101 min S/N: 331
15.372 min S/N: 773
14.574 min S/N: 108
12.311 min S/N: 115
13.579 min S/N: 245
Reconstructed ion chromatogram of a standard
(5ng of each analyte)
The mass spectra data is compared to the
reference standards to confirm the presence
of melamine.
The validated technique has been
successfully applied to Lactose samples,
amongst others, where the absence of
protein needs to be guaranteed.
Alternatives to USP
<461> Nitrogen Test
The USP <461> nitrogen test is based upon
the classical Kjeldahl method. This consists
of three distinct steps: Digestion, distillation
and titration.
The purpose of the digestion step is to use
sulfuric acid to break the material down and
convert the nitrogen present to Ammonia.
This distillation step is used to separate the
ammonia from the digestate for
determination by titration.
The method typically requires a gram of
material for analysis as well as significant
volumes of concentrated acids.
For more information on Melamine
Analysis or Nitrogen Chemiluminesence,
please contact:
Frank Judge
[email protected]
David Bell
[email protected]
Also available:
BLP01 - USP Residual Solvents
BLP02 - USP Heavy Metals
BLP03 - Elemental Analysis
BLP04 - CFC Analysis