title: Validation of an ultrasensitive LC-MS/MS method for PTH 1-34 in porcine plasma to support a solid dose PK study.
abstract: BACKGROUND
  The bioanalysis of Teriparatide (PTH 1-34) is extremely challenging due to the low plasma concentrations present at a therapeutic level. An LC-MS/MS-based method was developed that detected PTH 1-34 at 15 pg/ml in porcine plasma, and was validated using the bioanalytical method validation guidelines.
  
  
  RESULTS
  The analytical methodology demonstrated good linearity over a range of 15-1000 pg/ml, and demonstrated good precision and accuracy. The validated method was used to support a trial comparing a solid state dose to a solution-based injection (Forteo™).
  
  
  CONCLUSIONS
  The ability to quantify the peptide at low pg/ml in porcine plasma demonstrates that it is possible to develop very sensitive LC-MS/MS-based methodologies to support the bioanalysis of large peptide biotherapeutics.
authors.affiliation: LGC, Newmarket Road, Fordham, Cambridgeshire, CB7 5WW, UK.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Kay
authors.affiliation: LGC, Newmarket Road, Fordham, Cambridgeshire, CB7 5WW, UK.
authors.forename: Jonathan T
authors.initials: JT
authors.lastname: Hands
authors.affiliation: LGC, Newmarket Road, Fordham, Cambridgeshire, CB7 5WW, UK.
authors.forename: Glen
authors.initials: G
authors.lastname: Hawthorne
authors.affiliation: Quotient Bioresearch (Rushden) Ltd, Rushden, Northamptonshire, NN10 6EY, UK.
authors.forename: Scott
authors.initials: S
authors.lastname: Constable
authors.affiliation: Glide Pharma, Milton Park, Western Avenue, Abingdon, Oxfordshire, OX14 4RU, UK.
authors.forename: Martin
authors.initials: M
authors.lastname: Grosvenor
authors.affiliation: Glide Pharma, Milton Park, Western Avenue, Abingdon, Oxfordshire, OX14 4RU, UK.
authors.forename: Johannah A
authors.initials: JA
authors.lastname: Sharman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001774:Blood Chemical Analysis / Q000295:instrumentation* / Q000379:methods* / Q000592:standards; D050071:Bone Density Conservation Agents / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D006207:Half-Life; D008969:Molecular Sequence Data; D015203:Reproducibility of Results; D013552:Swine; D053719:Tandem Mass Spectrometry; D019379:Teriparatide / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
chemical_list: D050071:Bone Density Conservation Agents; D019379:Teriparatide