Triptorelin Technical Specification Sheet

Molecular Properties

Parameter Value
Chemical Name Triptorelin Acetate / [D-Trp⁶]-LHRH
Amino Acid Sequence pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH₂
Molecular Formula C₆₄H₈₂N₁₈O₁₃
Molecular Weight 1311.47 g/mol (free base); 1431.55 g/mol (acetate salt)
CAS Number 57773-63-4 (free base); 140194-24-7 (acetate)
Sequence Length 10 amino acids (synthetic GnRH superagonist)
Receptor Target GnRH receptor (GnRHR) on pituitary gonadotrophs

Physical Properties

Property Specification
Appearance White to off-white lyophilized powder
Solubility Freely soluble in water, PBS, or 0.9% saline at ≥2 mg/mL; pH 4.0-6.5
pH (1% solution) 5.0 - 6.5
Hygroscopicity Moderate; desiccated storage required
Solution Stability Stable at 4°C for 14-21 days (improved vs native GnRH)

Analytical Specifications

Test Specification
HPLC Purity ≥98.0%
Mass Spectrometry Confirmed [M+H]⁺ = 1311.47 ± 0.5 Da (free base)
Peptide Content ≥95% (by amino acid analysis)
Endotoxin Level <1.0 EU/mg
Acetate Content 8-12% (for acetate salt form)
TFA Content ≤0.1%
Water Content ≤6% (Karl Fischer)

Storage Parameters

Condition Specification
Lyophilized Storage -20°C to -80°C, desiccated, protected from light
Lyophilized Shelf Life 36 months when stored properly
Reconstituted Storage 2-8°C for up to 21 days; -20°C for up to 6 months
Reconstitution Protocol Add 1.0 mL sterile water or bacteriostatic water to 1 mg vial; gentle vortex 30-60 seconds
Freeze-Thaw Cycles Tolerates up to 5 cycles; stability superior to native GnRH
Light Sensitivity Minimal; standard amber vials recommended

Research Dosing Reference

Application Typical Dose Range Frequency Route
In Vitro Pituitary Cell Assays 0.1-10 nM (50-200x more potent than GnRH) Acute or chronic exposure Culture media
Small Animal Models (Rodent) 50-500 μg/kg Single dose or weekly depot SC injection
Receptor Desensitization Studies 100-200 μg/kg Single dose; monitor 7-21 days SC or IM
Gonadal Suppression Models 0.5-2 mg/kg (depot formulation) Monthly or every 3 months IM depot injection
Note: Dosing information is for research reference only. Triptorelin is intended for research purposes. Initial stimulation followed by downregulation occurs with chronic administration.

Key Research Studies

Year Study Focus Key Findings
1982 Superagonist potency characterization D-Trp⁶ substitution increased GnRHR binding affinity 50-100 fold vs native GnRH; demonstrated EC₅₀ of 0.01-0.05 nM for LH release from rat pituitary cells
1995 Pharmacokinetics and receptor dynamics Single SC dose (100 μg/kg) produced initial LH surge at 4h followed by sustained suppression for 14-28 days; receptor downregulation detected by day 7 with >80% reduction in GnRHR density
2004 Depot formulation development Biodegradable microsphere depot released triptorelin over 1-3 months; maintained therapeutic suppression with single injection; plasma levels 0.5-2 ng/mL sustained gonadal axis suppression
2012 Structure-activity and metabolic stability D-amino acid at position 6 conferred peptidase resistance; plasma half-life extended to 3-5 hours vs 2-4 minutes for native GnRH; metabolic stability increased 50-100 fold

Mechanism of Action

Biological Pathway Description
Receptor Binding High-affinity GnRHR agonist; Kd ~0.1-0.5 nM (50-100x higher affinity than native GnRH)
Initial Agonist Effect First 2-7 days: supraphysiological GnRHR activation → LH/FSH surge → transient increase in sex steroids
Receptor Downregulation Continuous GnRHR stimulation → receptor internalization and degradation → 70-90% reduction in receptor density by day 14
Gonadal Suppression Sustained receptor desensitization → loss of LH/FSH pulsatile secretion → hypogonadal state (castration levels)
Half-Life 3-5 hours (SC); depot formulations provide sustained release over weeks to months

Comparative Analysis: Triptorelin vs Native GnRH

Parameter Native GnRH (Gonadorelin) Triptorelin
Position 6 Amino Acid Gly (L-amino acid) D-Trp (D-amino acid)
Receptor Affinity (Kd) 1-5 nM 0.1-0.5 nM (50-100x higher)
Half-Life (SC) 2-4 minutes 3-5 hours (75-150x longer)
Potency (LH release EC₅₀) 0.5-2 nM 0.01-0.05 nM (50-200x more potent)
Clinical Effect Pulsatile stimulation Biphasic: initial surge then suppression
Dosing Frequency Pulsatile (hourly) required Daily to monthly (depot)

Quality Control Parameters

Test Method Acceptance Criteria
Appearance (visual) White to off-white powder; no discoloration
Chiral Purity (D-Trp⁶) D-isomer ≥99%; L-isomer <1% at position 6
RP-HPLC (purity) Main peak ≥98.0%; no single impurity >0.5%
ESI-MS (identity) [M+H]⁺ = 1311.47 ± 0.5 Da confirmed
Biological Activity ≥90% potency vs reference standard in LH release assay

External References

1. Engel JB, Schally AV. Drug Insight: clinical use of agonists and antagonists of luteinizing-hormone-releasing hormone. Nat Clin Pract Endocrinol Metab. 2007;3(2):157-67. https://pubmed.ncbi.nlm.nih.gov/17237843/

2. National Center for Biotechnology Information. PubChem Compound Summary for Triptorelin. https://pubchem.ncbi.nlm.nih.gov/compound/Triptorelin

3. Limonta P, et al. GnRH receptors in cancer: from cell biology to novel targeted therapeutic strategies. Endocr Rev. 2012;33(5):784-811. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3461332/

Disclaimer: This product is intended for research use only. Not for human or veterinary diagnostic or therapeutic use. Triptorelin causes initial hormonal flare followed by suppression.