Thyrotropin-Releasing Hormone (TRH)

1 Identity

Base synthetic tripeptide, three residues, all-L, no cysteine, no disulfide, no metal. Two covalent modifications carry the identity and neither is optional: a non-proteinogenic N-terminal pyroglutamate formed by cyclization of glutamine or glutamate, and a C-terminal primary amide on prolinamide. Small, highly polar and freely water-soluble at roughly 25 mg/mL, hygroscopic, melting above 143 degrees C with decomposition. No Trp, Tyr or Phe, so there is no 280 nm chromophore; histidine absorbs only weakly and near 211 nm. and by the sequence shorthand pGlu-His-Pro-NH2. The article is sold in this market under headings reading "Thyrotropin TRH", and thyrotropin is a different molecule of a different class entirely — see the variant note below.

Sequence

H-pGlu-His-Pro-NH2 (pyroglutamyl-L-histidyl-L-prolinamide). Three residues, all-L. The N-terminal pyroglutamate is a cyclization product and is part of the identity, not an impurity; the C-terminal is a primary amide and not a free acid. The molecule is small enough that a full residue-by-residue confirmation is cheap, which removes every excuse for a mass-only certificate. Both termini are the failure points: the amide hydrolyzes to the free acid at plus 0.984 Da, and the pyroglutamate can be delivered uncyclized at plus 18.011 Da.

Molecular formula

C16H22N6O4 (free base), CAS 24305-27-9. Mono-acetate salt C18H26N6O6. Free-acid degradation product C16H21N5O5.

Average mass

362.390 Da (C16H22N6O4), computed on IUPAC 2021 abridged conventional atomic weights from the formula stated. A chemical reference database prints 362.38 for the same formula and CAS on the older table, and the two agree within rounding; the basis is stated on the face of the number because this catalog standardizes on the 2021 table. Mono-acetate salt 422.442 Da; the free base is 85.8 percent of the salt by mass, which is the correction a labeled-milligram figure needs and rarely gets on a molecule this small, where the counterion is a large fraction of the weight.

Monoisotopic mass

362.17025 Da neutral (C16H22N6O4); [M+H]+ 363.17753; [M-H]- 361.16297. A plus or minus 5 ppm window on [M+H]+ is plus or minus 0.0018 Da. At 362 Da the plus 0.984 Da amide-to-acid difference is 2,700 ppm and is trivially resolved by any instrument, which is exactly why a certificate that does not report it has chosen not to look.

Salt / variant note

A small molecule with a large substitution surface, because both termini are labile and the name collides with a different class of article entirely. All figures computed on the IUPAC 2021 abridged table. The class collision is the more expensive of the two mistakes, and it comes first: thyrotropin (TSH) is a heterodimeric glycoprotein of roughly 28 to 30 kDa, and thyrotropin alfa is recombinant human TSH, a licensed biological product marketed as Thyrogen. A catalog heading reading "Thyrotropin" with "TRH" beside it names two articles roughly eighty-fold apart in mass, one a 362 Da synthetic tripeptide and one a licensed glycoprotein biologic, and no purity figure reconciles them. Terminus variants, both invisible to a nominal-mass method that reports one integer: the C-terminal free acid, pGlu-His-Pro-OH, C16H21N5O5, 363.374 / 363.15427, exactly plus 0.984 Da, the amide-hydrolysis product and the single most likely defect; and the uncyclized N-terminus, H-Glu-His-Pro-NH2, C16H24N6O5, 380.405 / 380.18082, plus 18.011 Da, which is incomplete pyroglutamate formation rather than degradation. Degradation and fragment species: cyclo(His-Pro) diketopiperazine, C11H14N4O2, 234.259 / 234.11168, the documented cyclization product of the C-terminal dipeptide; des-pGlu H-His-Pro-NH2, C11H17N5O2, 251.290 / 251.13822. Chain-extension species: pGlu-His-Pro-Gly-OH, C18H24N6O6, 420.426 / 420.17573, the glycine-extended form. Separate molecules sold under adjacent names: taltirelin, C17H23N7O5, 405.415 / 405.17607, a synthetic analog marketed in Japan and not this article; montirelin and azetirelin likewise. Stereochemical substitution, the one no mass detects: D-His at position 2 gives an identical formula and identical exact mass at every decimal place, and only a chiral method or a validated chromatographic separation finds it. Salt form: mono-acetate C18H26N6O6, 422.442, of which the free base is 85.8 percent by mass, a correction large enough on a 362 Da molecule to move a labeled-milligram figure materially.

2 Class & testing panel

Form

Single article

Testing panel

P1 — panel definitionfollowing this catalog's convention that an all-L peptide whose only non-proteinogenic feature is an N-terminal pyroglutamate stays on the base panel, with the pyroglutamate and the C-terminal amide both written as identity attributes rather than as related substances. The assignment follows the residue chemistry: this is an all-L pyroglutamyl peptide carrying no D-residue, the same basis on which gonadorelin sits at P1, where alarelin sits at P3 because it carries a D-residue

3 Primary sources & evidence

The index reports the design and provenance of the literature, not a conclusion about effect.

A large primary literature exists. This record states less about the compound than it merits, because an unverified identifier is worse than none and these identifiers were not verified. What is verified and recorded: the substance was characterized as a synthetic tripeptide of defined structure and has been the subject of published work continuously since the late 1960s; a synthetic analog, taltirelin, is separately marketed in Japan; and the substance held a United States marketing approval, NDA 018087, from Ferring Pharmaceuticals, withdrawn effective 17 November 2014 on administrative grounds and expressly not for reasons of safety or effectiveness, per the Federal Register notice at docket FDA-2013-N-1285 and the withdrawal notice of 17 November 2014. A DailyMed record exists for a protirelin 500 microgram per 1 mL solution from AnazaoHealth Corporation in the "unapproved drug other" marketing category, NDC 51808-209-01, now inactivated.

4 Storage & specification

Storage

Lyophilized or crystalline solid in the sealed original vial, minus 20 degrees C plus or minus 5 degrees C, desiccated, protected from light. The material is hygroscopic and freely water-soluble at roughly 25 mg/mL, so vials are equilibrated to room temperature before the seal is broken and are not left open on the bench; water uptake shows up directly in the Karl Fischer result and indirectly in every content figure calculated from weight. Reference standards and retains at minus 80 degrees C plus or minus 10 degrees C.

Shelf life

The provisional retest interval is 24 months at minus 20 degrees C plus or minus 5 degrees C in the sealed original container, pending the company's own stability data. The interval is dated on the two termini rather than on gross purity, because both moves are small and specific: hydrolysis of the C-terminal amide at plus 0.984 Da, and formation of cyclo(His-Pro) at 234.11168 with the corresponding loss of parent. The stability-indicating method must resolve the free acid from parent, which an area-percent figure on an unresolved pair will not do.