Intact Teriparatide (PTH 1-34) measurement in human plasma by microflow ionKey LC-MS/MS

Tang, Jonathan C. Y. ORCID:, Dunn, Rachel, Barnes, Simon and Fraser, William (2022) Intact Teriparatide (PTH 1-34) measurement in human plasma by microflow ionKey LC-MS/MS. In: ASBMR 2022 annual meeting, 2022-09-09 - 2022-09-12.

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Background: Teriparatide, a recombinant human parathyroid hormone fragment 1–34 (hPTH 1-34) is an osteoanabolic agent for treatment of osteoporosis. The effect on bone decreases the risk of vertebral and non-vertebral fractures and increases bone mineral density (BMD) in post-menopausal women with osteoporosis. Biosimilars of teriparatide are expected to rise; pharmacokinetic studies require the determination of plasma concentrations to evaluate bioequivalence and optimise formulation strategies. Method: An LC-MS/MS was developed on the Waters Acquity M-Class microflow UPLC system coupled to the Xevo TQ-XS mass spectrometer with IonKey source (Milford, MA, USA). Intact hPTH 1-34 was detected on [M+6]6+ ions at m/z transition 687>787, using rat PTH 1-34 as internal standard at m/z 580>648. hPTH 1-34 in EDTA plasma samples obtained from human subjects given a single 20 µg dose of Teriparatide (n=890) (Fortsteo, Eli Lilly, IN, USA) was extracted using a Waters Oasis® HLB µElution plate, and further enriched by online trapping. Bioanalytical validation on the new method was carried out, results were compared with our established standard flow LC-MS/MS method, which was cross-validated against immunoassay (IDS; Boldon Tyne and Wear. UK). Results and Discussion: LC-MS/MS produced a linear calibration curve from 10 to 2000 pg/mL (r2 >0.990). The LLoQ and LLoD for PTH 1-34 were 5 pg/mL and 2.1 pg/mL, respectively. The inter- /intra-assay precision (CV%) of the method were <9.7 and <8.2% and accuracy of >98.3% for four QCs (60, 100, 200, and 800 pg/mL). The mean recovery of PTH 1-34 was 107.2%. Our method was successfully applied to quantify PTH 1-34. Pharmacokinetic profiles showed rapid absorption of PTH 1-34 in plasma. The average maximal plasma concentration (Cmax), time to maximal exposure (Tmax), systemic exposure (AUC0-last) and plasma clearance (T½) was 271 pg/mL, 16.0±2.5 min, 190 pg*min/mL, 37.7±6.8 min, respectively. Conclusion: We have improved upon our Intact LC-MS/MS assay using microflow IonKey LC-MS/MS technique. Direct detection of teriparatide with a limit of quantitation of 5 pg/mL was achieved, with good precision and accuracy, excellent analyte recovery, and negligible matrix effects. The method has successfully analysed hPTH 1-34 in large pharmacokinetic studies, demonstrating its robustness and throughput.

Item Type: Conference or Workshop Item (Poster)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Musculoskeletal Medicine
Faculty of Medicine and Health Sciences > Research Centres > Metabolic Health
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Depositing User: LivePure Connector
Date Deposited: 27 Apr 2023 14:30
Last Modified: 19 Oct 2023 04:03

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