Validation of an ultrasensitive LC–MS/MS method for PTH 1–34 in porcine plasma to support a solid dose PK study. (July 2015)

• Record Type: Journal Article
• Authors: Kay, Richard G; Hands, Jonathan T; Hawthorne, Glen; Constable, Scott; Grosvenor, Martin; Sharman, Johannah A
• Is Part Of: Bioanalysis. Volume 7:Number 12(2015)
• Page Start: 1435
• Page End: 1445
• Publication Date: 2015-07
• Subjects: Drugs -- Analysis -- Periodicals; 615.19005
• DOI: 10.4155/bio.15.75
• Languages: English
• ISSNs: 1757-6180

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™).Conclusion: 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.