1 Certainty of Identification in Certainty of Identification in Pharmaceutical and Forensic Pharmaceutical and Forensic Mass Spectrometry Mass Spectrometry Phil Teale, HFL Ltd. About HFL • The only laboratory in the world engaged in sports doping control & contract research • Long heritage in high integrity analysis & centralised laboratory services (est. 1963) • 130 people • State-of-the-art facilities (1997) near Cambridge • Leader in development & validation of difficult analytical methods in complex matrices • Quality focus Markets & services Sports • Drug surveillance – Animal sports Animal sports – Human sports Human sports • Sports research – WADA WADA – HBLB HBLB – NGRC NGRC – UK Sport UK Sport • Veterinary Government Healthcare Pharma Sports Markets & services Pharma • In vitro discovery • Bioanalysis • Biomarkers • Central clinical laboratory • Pharmaceutical analysis Sports Government Healthcare Pharma Qualitative MS: Pharmaceutical Applications • NCE synthesis and development • Metabolite identification / characterisation • Impurity identification / characterisation • Patent protection Regulatory Framework • FDA / GLP • Multiple analytical platforms (accurate mass, NMR, etc.) • Verification against standards, including isomers • Typically no industry generic MS criteria • Expert user / Peer review Certainty of Identification in Pharmaceutical and Forensic Mass Spectrometry Applications Phil Teale - HFL, Fordham
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Certainty of Identification in Certainty of Identification in Pharmaceutical and Forensic Pharmaceutical and Forensic
Mass SpectrometryMass SpectrometryPhil Teale, HFL Ltd.
About HFL• The only laboratory in the world engaged in sports doping
control & contract research• Long heritage in high integrity analysis & centralised laboratory
services (est. 1963)• 130 people• State-of-the-art facilities (1997) near Cambridge• Leader in development & validation of difficult analytical
methods in complex matrices• Quality focus
Markets & services
Sports• Drug surveillance
–– Animal sports Animal sports –– Human sportsHuman sports
• Sports research–– WADAWADA–– HBLBHBLB–– NGRCNGRC–– UK SportUK Sport
• Veterinary
Government
HealthcarePharma
Sports
Markets & services
Pharma• In vitro discovery• Bioanalysis• Biomarkers• Central clinical
laboratory• Pharmaceutical
analysis
Sports
GovernmentHealthcare
Pharma
Qualitative MS: Pharmaceutical Applications
• NCE synthesis and development• Metabolite identification /
characterisation• Impurity identification /
characterisation• Patent protection
Regulatory Framework
• FDA / GLP• Multiple analytical platforms
(accurate mass, NMR, etc.)• Verification against standards,
including isomers• Typically no industry generic MS
criteria • Expert user / Peer review
Certainty of Identification in Pharmaceuticaland Forensic Mass Spectrometry Applications
Phil Teale - HFL, Fordham
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Forensic Applications
• Illicit drug identification (including source)
• Sample characterisation and comparison
• Toxicology (poisoning and illicit use)• Sports / residue testing
Regulatory Framework
• ISO 17025
• Process driven (detailed SOP’s)• Consistent reporting• Criteria for identification are a
requirement
Process (Confirmatory)
• Instrumental criteria, maintenance, calibration, response, etc.
• Sample prep SOP• Sample type and running order• MS acceptance criteria
Industry Criteria
• FDA / EU residue testing (mandatory)
• WADA / AORC sports testing (advisory)
• Drive for ISO 17025 accreditation• Lab to lab consistency• Protection from legal challenge
AORC Criteria
• Retention time
• GC - 1% (RRT or RT) or 6 sec (RT)
• LC - 2% (RRT or RT) or 12 sec (RT)
MS Criteria
• Requires 3 diagnostic ions (criteria advise but are not specific).
• Single-stage MS: 10% absolute or 30% relative, whichever is the greater
• MS/MS & related techniques: 20% absolute or 40% relative, whichever is the greater.
Certainty of Identification in Pharmaceuticaland Forensic Mass Spectrometry Applications
Phil Teale - HFL, Fordham
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Full-scan
single-stage MS: Full-scan MS/MS
& related techniques:
R.A. of matched ion in reference
spectrum Acceptable R.A. in test spectrum (10% absolute
or 30% relative)
Acceptable R.A. in test spectrum (20% absolute
or 40% relative) 100% 70-100 (90-100)1 60-100 (85-100)2