Detection of myo‐inositol tris pyrophosphate (ITPP) in equine following an administration of ITPP

Abstract

Myo-Inositol tris pyrophosphate (ITPP) is a powerful allosteric modulator of haemoglobin that increases oxygen-releasing capacity of red blood cells. It is capable of crossing the red blood cell membrane unlike its open polyphosphate analog myo-inositol hexakisphosphate (IHP). Systemic administration of ITPP enhanced the exercise capacity in mice. There have been rumours of its abuse in the horse racing industry to enhance the performance of racing horses. In this paper, the detection of ITPP in equine plasma and urine after an administration of ITPP is reported. A Standardbred mare was administered 200 mg of ITPP intravenously. Urine and plasma samples were collected up to 120 h post administration and analyzed for ITPP by liquid chromatography-tandem mass spectrometry. ITPP was detected in post administration plasma samples up to 6 hours. The peak concentration was detected at 5 min post administration. In urine, ITPP was detected up to 24 h post administration. The peak concentration was detected at 1.5 h post administration.

Screening and confirmation of myo‐inositol trispyrophosphate (ITPP) in human urine by hydrophilic interaction liquid chromatography high resolution / high accuracy mass spectrometry for doping control purposes

“…When subjected to an NCE of 30% the doubly charged precursor ions dissociated leading to singly charged product ions that correspond either to different phosphate moieties at m/z 78.9580 (PO 3 − ), m/z 158.9243 (HP 2 O 6 − ), and m/z 238.8906 (H 2 P 3 O 9 − ) or to the myo‐inositol scaffold at m/z 444.8886 and m/z 524.8550 for ITPP, and m/z 450.9263 and m/z 530.8926 for ITPP‐d6, that were generated by the loss of metaphosphate ( m/z 78.9580; PO 3 − ) or pyrophosphate ( m/z 158.9243; HP 2 O 6 − ), respectively. Our results, based on accurate mass measurements, are in accordance with proposed collision‐induced fragmentation pathways of ITPP and its hexadeuterated analogue in recent publications …”

“…9580 collision-induced fragmentation pathways of ITPP and its hexadeuterated analogue in recent publications. [22,29]…”

Exercise Induced Changes in Salivary and Serum Metabolome in Trained Standardbred, Assessed by 1H-NMR

“…Myo-inositol is also the most effective allosteric effector identified to date, being able to increase the tissue delivering of oxygen bound to hemoglobin [54]. Since its administration can improve sport performance in laboratory mice, its analogues have been suspected to be abused in the horse racing industry [55]. Up to now, no study about its effect in equine species has been performed.…”

Respiratory metabolites in bronchoalveolar lavage fluid (BALF) and exhaled breath condensate (EBC) can differentiate horses affected by severe equine asthma from healthy horses

“…Myo-inositol is also the most effective allosteric effector identified to date, being able to increase the tissue delivering of oxygen bound to hemoglobin [29]. Since its administration can improve sport performance in laboratory mice, its analogues have been suspected to be abused in horse racing industry [30] but no study about its effect in equine species has been performed. In our opinion, further research about myo-inositol function and its efficacy as therapeutic tool in horses with respiratory diseases should be performed.…”