LC-MS/MS measurement of parathyroid hormone PTH (1-34): Use in studying oral PTH (1-34) administration and possible diagnostic application in pseudohypoparathyroidism.

Al Riyami, Sulaiman, Tang, Jonathan C Y, Galitzer, Hillel and Fraser, William (2017) LC-MS/MS measurement of parathyroid hormone PTH (1-34): Use in studying oral PTH (1-34) administration and possible diagnostic application in pseudohypoparathyroidism. In: Society for Endocrinology BES 2017, 2017-11-06 - 2017-11-08.

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Abstract

Background: Teriparatide PTH(1-34) is an osteoanabolic agent used in the treatment of osteoporosis. Measurement of PTH(1-34) can be useful in osteoporosis treatment and in the diagnosis of pseudohypoparathyroidism (PHP) by confirming administration of PTH(1-34) Aims: 1) To assess PTH(1-34) profiles obtained using standard Forsteo treatment compared to using a novel oral administration. 2) To confirm the PTH(1-34) in a PHP patient receiving PTH(1-34) as part of an Ellsworth Howard Test (EHT). 3) To perform a method comparison of oxidised/non oxidised forms of PTH(1-34) detected by LC-MS/MS with immunoassay. Methods: Using a LC-MS/MS method, PTH(1-34) was measured in Pharmacokinetic (PK) profiles from a human double blinded study. Participants were given teriparatide either by a single SC injection (Forsteo,20µg) (n=6); or in an oral dose of 0.69mg (n=4), or 2.07mg (n=6) (EnteraBio). In an EHT, PTH(1-34), urinary PO4, and urine/plasma cyclic adenosine 3’5’-monophosphate (cAMP) were measured on samples before/after 20µg Forsteo injection. Oxidised/non-oxidised forms of PTH(1-34) (n=390) measured by LC-MS/MS were compared against immunoassay (IDS; Boldon, UK). Results: PK profiles showed rapid absorption of PTH(1-34) in plasma. The 2.07 mg oral dose achieved Cmax of 271pg/mL comparable to that of 20µg Forsteo, but the injection form showed slower rate of plasma clearance (T½(injection)¬=37.7min, T½(oral)=12.5min). The EHT profile from a PHP patient showed a lack of cAMP response despite significant increase in plasma PTH(1-34) concentration. Method comparison showed LC-MS/MS results were correlated (r2=0.950), but biased (-35.5%) against the immunoassay. The bias was caused partly by a matrix effect (14.6±18.4%), cross reactivity of the immunoassay with PTH(1-84) (7.1±0.45%) and to oxidised forms of PTH(1-34) (23.9±6.1%). Conclusion: Our LC-MS/MS method for PTH(1-34) can help validate the therapeutic use of osteoanabolic agents; confirm the lack of response to exogenous stimulation in EHT; and may explain the differences in responses to treatment due to oxidation of PTH(1-34).

Item Type: Conference or Workshop Item (Poster)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 16 Nov 2017 06:09
Last Modified: 11 Apr 2019 15:15
URI: https://ueaeprints.uea.ac.uk/id/eprint/65475
DOI: 10.1530/endoabs.50.P042

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