Gonadorelin (GnRH)

1 Identity

Synthetic linear decapeptide, identical to the native human hypothalamic releasing hormone. C-terminally amidated, N-terminally pyroglutamated. The active moiety of two discontinued US human drug products and of currently marketed veterinary products. US human trade names, both discontinued: Factrel, gonadorelin hydrochloride, NDA 018123.

Sequence

PGlu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2. Ten residues. All chiral centers are L and every residue is constitutionally proteinogenic; the N-terminal pyroglutamate is an intramolecular cyclization of the L-glutamate residue — a five-membered lactam formed between the side-chain carboxyl and the alpha-amino nitrogen — and not a foreign building block, so it retains L configuration and does not by itself trigger P3. The C-terminus is a primary carboxamide on Gly10, not a free acid. There is no free N-terminal amine: the pyroglutamate lactam consumes it, which is why the molecule fails Edman degradation and why sequence confirmation on this article is done by MS/MS rather than by N-terminal sequencing. MS/MS is mandatory here, and an N-terminal sequencing result offered on this article is evidence that something else was tested. No cysteine and therefore no disulfide. No acylation, no lipidation, no PEGylation, no metal center, no glycosylation. The formula and both masses on this record are derived from this sequence and are internally consistent with it rather than restated from a primary chemical-database entry, so a signed supplier structure declaration and primary-registry confirmation are conditions of the first lot. No CAS number is stated for this article.

Molecular formula

C55H75N17O13 (free base). Acetate salt C55H75N17O13 . C2H4O2 = C57H79N17O15. Hydrochloride C55H76ClN17O13.

Average mass

1182.311 Da for the free base C55H75N17O13, from the formula on IUPAC 2021 abridged conventional atomic weights. Listings commonly print 1182.31; the formula gives 1182.311. Acetate salt 1242.36 Da; hydrochloride 1218.77 Da. The figure is a reconstruction from the stated sequence and not a restatement of a supplier number, and it stands or falls with that sequence, which is why a written structure declaration is a first-lot condition.

Monoisotopic mass

1181.5730 Da neutral. [M+H]+ 1182.5803; [M+2H]2+ 591.7938, which is the ion a routine LC-MS identity test on a decapeptide will actually report; [M+3H]3+ 394.8650; [M-H]- 1180.5657. Acetate salt 1241.5942 neutral.

Salt / variant note

(1) Free base C55H75N17O13, 1182.31 / 1181.5730. (2) acetate salt C57H79N17O15, 1242.36 / 1241.5942, +60.05 Da — the salt of the discontinued Lutrepulse article and the commonest research presentation, so a quoted 1242 is a salt mass and not a heavier peptide. (3) hydrochloride C55H76ClN17O13, 1218.77 / 1217.5497, +36.46 Da — the salt of the discontinued Factrel article. (4) Gonadorelin free acid, des-amide, C55H74N16O14, 1183.30 / 1182.5570, +0.98 Da — the commonest specified impurity, and invisible to any tolerance stated in whole daltons. (5) the open-chain precursor: the linear glutamyl form in which the N-terminal pyroglutamate has failed to cyclize, C55H77N17O14, 1200.33 / 1199.5836, +18.02 Da — a real process impurity, carried as a specified impurity on this record, and the direct signature of an incomplete cyclization step. (6) des-Gly10 nonapeptide amide C53H72N16O12, 1125.26 / 1124.5516, -57.05 Da. (7) the registered medicines in the same class, every one of which is a different molecule that would be shipped against a GnRH order: triptorelin ([D-Trp6]) C64H82N18O13, 1311.47 / 1310.6309, +129.16 Da — a separate record in this catalog; leuprolide C59H84N16O12, 1209.42 / 1208.6455, +27.11; buserelin C60H86N16O13, 1239.45 / 1238.6560, +57.14; goserelin C59H84N18O14, 1269.43 / 1268.6414, +87.12. (8) Oxidation on the single tryptophan: +16 and +32 Da, 1198.31 and 1214.31 average. (9) the substitution mass cannot reach: any single-center epimer of this all-L decapeptide is exactly isobaric and co-elutes on an achiral reversed-phase column, and histidine and serine are the residues most prone to racemization during chain assembly.

2 Class & testing panel

Form

Single article

Testing panel

P1 — panel definition

3 Primary sources & evidence

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

Published literature exists and the index grades it C: small or preliminary human data only, on the express reasoning that decades of genuine human clinical evidence exist but come largely from uncontrolled cohorts and case series rather than randomized controlled trials, and apply to pump-delivered pulsatile administration. Identifiers and study types. Balasubramanian R, Crowley WF Jr, "Isolated Gonadotropin-Releasing Hormone (GnRH) Deficiency", GeneReviews 2007, updated 2022, PMID 20301509 — human genetic and physiological synthesis. Young J, Xu C, Papadakis GE, Acierno JS, Maione L, Hietamaki J, Raivio T, Pitteloud N, "Clinical Management of Congenital Hypogonadotropic Hypogonadism", Endocr Rev 2019, PMID 30698671 — authoritative expert review synthesizing decades of human data, largely from uncontrolled cohorts and case series rather than RCTs. Bettocchi C, Rinaldi M, Sebastiani F, Curr Pharm Des 2021, PMID 33238870, and Pitteloud N, Dwyer A, Ann Endocrinol (Paris) 2014, PMID 24793994 — reviews of human clinical experience. Regulatory documents in Drugs@FDA and openFDA: FACTREL, gonadorelin hydrochloride, NDA 018123, sponsor Hikma, originally approved 30 September 1982, all strengths (0.1 mg, 0.2 mg, 0.5 mg per vial) marketing status Discontinued; LUTREPULSE KIT, gonadorelin acetate, NDA 019687, sponsor Ferring, originally approved 10 October 1989, both strengths (0.8 mg, 3.2 mg per vial) marketing status Discontinued. Stated as an absence: a targeted PubMed query in the context of testosterone replacement and fertility in men returned 13 records, none of which described gonadorelin administered intermittently alongside testosterone replacement. No such trial was identified, and an absence of this kind cannot prove that none exists anywhere. Delivery pattern is the determining experimental variable, which is a fact about how the studies were designed.

4 Storage & specification

Storage

White to off-white lyophilized powder in a Type I amber glass vial with a PTFE-lined closure; a laboratory-chemical presentation, not a stoppered and crimped injection vial, with no sterility claim. Store at -20 degrees C plus or minus 5 degrees C, desiccated, tightly closed, protected from light — the single tryptophan indole and the tyrosine phenol make the solid photolabile and oxidation-sensitive. Hygroscopic as the acetate salt; the arginine guanidinium and the histidine imidazole both take up water. Equilibrate the sealed vial to ambient temperature before opening so that atmospheric moisture does not condense onto the cake. Reconstituted solution is aliquoted single-use and held at -80 degrees C; the native molecule's circulating half-life is short, which is a solution-stability warning as much as anything else, and repeated freeze-thaw is prohibited on the label rather than merely discouraged. Ships ambient with a labeled cumulative excursion allowance and a single-use temperature logger in every export carton. Segregated from triptorelin and from every other GnRH-class article at the weighing bench, because five molecules in this family carry near-identical trade descriptions and differ in mass by amounts a nominal-resolution instrument will not resolve reliably.

Shelf life

Provisional 24 months at -20 degrees C plus or minus 5 degrees C, desiccated and protected from light, from the date of QA release, stated as provisional pending the company's own stability data. Stability-indicating attributes: tryptophan-oxidation products at +16 and +32 Da, the des-amide free acid, the uncyclized open-chain precursor, total related substances and Karl Fischer water. Real-time pulls at 3, 6, 9, 12, 18 and 24 months at the labeled condition plus 6 months accelerated at 40 degrees C and 75 percent relative humidity, with an ICH Q1B photostability challenge run once on the launch lot in the final container. Extension beyond 24 months only on real-time data from three commercial lots. Printed retest date on every vial and first-expiry-first-out enforced against that date rather than against receipt date.