Product Overview

Melatonin (INCI: Melatonin, N-Acetyl-5-methoxytryptamine, CAS 73-31-4, C₁₃H₁₆N₂O₂, MW 232.28 g/mol) is an endogenous indoleamine hormone primarily synthesized in the pineal gland through the biosynthetic pathway: tryptophan → 5-hydroxytryptophan (5-HTP) → serotonin → N-acetylserotonin (NAS) → melatonin, catalyzed by arylalkylamine N-acetyltransferase (AANAT, rate-limiting) and hydroxyindole-O-methyltransferase (HIOMT). Melatonin acts as the body’s master circadian pacemaker through MT1 and MT2 G-protein coupled receptors (G₁-protein coupled) localized in the suprachiasmatic nucleus (SCN) of the hypothalamus — the brain’s central biological clock. The receptor signaling cascade proceeds as: MT1/MT2 receptor activation → G₁-protein dissociation → adenylyl cyclase inhibition → intracellular cAMP ↓ → PKA activity ↓ → CREB phosphorylation ↓ → transcriptional regulation of clock genes (PER1, PER2, CRY1, CRY2, BMAL1, CLOCK). This signaling cascade entrains the endogenous ~24.2-hour human circadian period to the environmental 24-hour light-dark cycle. Synthetic melatonin is chemically and structurally identical to endogenous human melatonin — it is the exact same molecule (C₁₃H₁₆N₂O₂), produced under pharmaceutical cGMP conditions rather than by the pineal gland, ensuring identical receptor binding kinetics, metabolism, and physiological effects. Melatonin is highly amphiphilic — possessing both hydrophilic (5-methoxy, acetamide side chain) and lipophilic (indole ring) domains — enabling passive diffusion across all biological barriers including the blood-brain barrier and placental barrier, a property unique among endogenous antioxidants. A defining feature of melatonin physiology is its selective mitochondrial concentration: melatonin is concentrated approximately 100× higher in the mitochondrial matrix versus the cytosol, a gradient maintained by oligopeptide transporters (PEPT1/2) in the inner mitochondrial membrane — providing targeted antioxidant protection at the cell’s primary ROS generation site. Extrapineal melatonin synthesis occurs in the gut (enterochromaffin cells, 400× pineal melatonin content), skin (epidermal keratinocytes and melanocytes expressing full tryptophan→melatonin enzymatic machinery), retina (photoreceptor cells), bone marrow, lymphocytes, and the Harderian gland — establishing melatonin as both a central circadian hormone and a local paracrine/autocrine protective molecule. UPOR Biotech provides melatonin in three grades: Pharma grade (≥99.5% HPLC, USP/EP monograph compliant) with Type II DMF support, Nutraceutical/Cosmetic grade (≥99% HPLC) for dietary supplements and topical formulations, and Micronized grade (D90 ≤10 µm) for enhanced oral absorption.

As a premier melatonin manufacturer and bulk supplier, UPOR Biotech serves the global sleep supplement market — a $5 billion+ industry with double-digit annual growth driven by increasing insomnia prevalence, aging demographics, and consumer shift toward non-habit-forming sleep solutions. Melatonin’s pharma-grade USP/EP positioning opens dual-market access: Rx pharmaceutical products (Circadin-class prolonged-release formulations, pediatric sleep disorder medications) and premium dietary supplements with pharmaceutical-quality differentiation. The topical cosmetic melatonin trend represents an emerging high-growth segment — anti-aging night creams, serums, and sleep masks incorporating melatonin at 0.01–0.1% for overnight cutaneous circadian alignment, DNA repair, and antioxidant protection — projected to reach $150M+ globally by 2028. Sustained-release innovation — hydrophilic matrix and polymer-based SR technologies that mimic the endogenous pineal secretion profile (gradual nocturnal rise, plateau, decline) — is the defining formulation frontier, enabling products that maintain therapeutic plasma levels for 6–8 hours versus 2–3 hours for immediate release. OEM and private label formulations available with flexible MOQ starting at 1 kg. Free sample available for qualified buyers. Every shipment includes full documentation: COA, MSDS, HPLC chromatogram, USP/EP compliance certificate (pharma grade), and stability data.

Melatonin vs 5-HTP vs GABA — The Sleep Support Hierarchy: Why Melatonin Is the Master Circadian Pacemaker

Comparing these three widely used sleep support ingredients reveals a clear mechanistic hierarchy — not interchangeability. GABA (gamma-aminobutyric acid) is the brain’s primary inhibitory neurotransmitter — it promotes relaxation and sleep onset by reducing neuronal excitability via GABA-A receptor chloride channel activation. However, GABA’s mechanism is downstream, non-specific sedation: it does not address the body’s circadian clock, and oral GABA’s blood-brain barrier penetration remains scientifically debated. 5-HTP (5-hydroxytryptophan) is a serotonin precursor — one step upstream of serotonin in the melatonin synthesis pathway (tryptophan → 5-HTP → serotonin → NAS → melatonin). 5-HTP increases serotonin availability, which can improve mood and sleep onset latency, but serotonin itself is not a circadian signal — it is a neurotransmitter with broad effects on mood, appetite, and cognition, and excess serotonin can compete with melatonin at receptor sites. Melatonin is unique: it is the body’s endogenous circadian pacemaker hormone — the direct molecular signal that tells the SCN and peripheral clocks “it is nighttime.” MT1 receptor activation inhibits neuronal firing in the SCN (sleep promotion), while MT2 receptor activation phase-shifts the circadian clock (entrainment). Unlike GABA (sedation without circadian reset) and 5-HTP (serotonin precursor, indirect), melatonin directly entrains the master biological clock. The clinical implication: for true circadian rhythm disorders (jet lag, shift work, delayed sleep phase syndrome), only melatonin provides chronobiotic correction — GABA and 5-HTP are symptomatic sleep aids that do not reset the circadian pacemaker. For formulation strategies, the melatonin + 5-HTP combination can be synergistic: 5-HTP provides the serotonergic substrate for endogenous melatonin synthesis, while exogenous melatonin provides immediate circadian signal delivery. Melatonin is the only ingredient in this hierarchy that is both the circadian master signal AND a master physiological antioxidant.

Technical Specifications

PropertySpecification
Product NameMelatonin Powder — Pharma Grade (≥99.5% USP/EP) / Nutraceutical/Cosmetic Grade (≥99%) / Micronized Grade
INCI NameMelatonin
CAS Number73-31-4
Molecular FormulaC₁₃H₁₆N₂O₂
Molecular Weight232.28 g/mol
SynonymsN-Acetyl-5-methoxytryptamine; MEL; Melatonine; Circadin; 5-Methoxy-N-acetyltryptamine; N-[2-(5-Methoxy-1H-indol-3-yl)ethyl]acetamide
SourceSynthetic — bioidentical to endogenous human pineal hormone; pharmaceutical grade
AppearanceWhite or slightly yellowish crystalline powder
Assay (Pharma Grade)≥99.5% (HPLC, anhydrous basis) — USP/EP monograph compliant
Assay (Nutraceutical/Cosmetic Grade)≥99.0% (HPLC, anhydrous basis)
IdentificationIR spectrum conforms to USP/EP Melatonin RS; HPLC retention time matches reference standard; UV λmax 278 nm (ethanol)
Melting Point116 – 120°C (USP/EP)
Loss on Drying≤0.5% (105°C, 2 hours)
Residue on Ignition≤0.1%
Related Substances — Individual Impurity (Pharma)≤0.10% any single unspecified impurity; ≤0.15% any specified impurity (HPLC, USP/EP)
Related Substances — Total Impurities (Pharma)≤0.5% total impurities (HPLC)
Related Substances (Nutraceutical Grade)Individual impurity ≤0.30%; Total impurities ≤1.0% (HPLC)
Heavy Metals (Total)≤10 ppm (as Pb)
Elemental ImpuritiesPb ≤2 ppm; As ≤1 ppm; Hg ≤1 ppm; Cd ≤1 ppm (USP <232> / ICH Q3D compliant, pharma grade)
Residual SolventsUSP <467> / EP <5.4> / ICH Q3C Class 3 compliant; quantitative GC-HS profile provided per batch (pharma grade)
Microbial LimitsTAMC ≤100 CFU/g; TYMC ≤10 CFU/g (USP <61> / EP <2.6.12>); Pathogens (E. coli, Salmonella, S. aureus, P. aeruginosa) — Absent in 10 g (USP <62> / EP <2.6.13>)
Micronized Particle Size (Optional)D90 ≤10 µm; D50 ≤5 µm (laser diffraction, Malvern)
Release ProfilesImmediate Release (standard powder); Sustained Release (hydrophilic matrix/polymer-based, 6–8 hour plasma profile)
SolubilitySoluble in ethanol (~8 mg/mL at 25°C), DMSO (~46 mg/mL), DMF (~30 mg/mL); sparingly soluble in water (~0.1 mg/mL at 25°C); slightly soluble in propylene glycol
pH (1% in Ethanol/Water 1:1)5.0 – 7.0
Grade / StandardsPharma Grade (≥99.5%, USP/EP monograph) / Nutraceutical/Cosmetic Grade (≥99%, HPLC) / Micronized Grade (enhanced absorption)
CertificationsISO 9001:2015, ISO 22000, HACCP, FDA Facility Registration, HALAL, KOSHER, Non-GMO, BSE/TSE-Free
Packaging1 kg / 5 kg / 10 kg sealed aluminum foil bags with PE liner; 25 kg fiber drums with double PE liner; light-protective outer packaging (amber/UV-barrier)
Storage2 – 8°C (refrigerated), tightly sealed in original container, protect from light and moisture
Shelf Life2 years from date of manufacture under recommended storage conditions

Key Benefits — Melatonin

MT1/MT2 Circadian Rhythm Regulation — Master Circadian Pacemaker

Melatonin is the body’s endogenous circadian pacemaker hormone — the direct molecular signal of darkness. MT1 receptor activation (G₁-protein → adenylyl cyclase ↓ → cAMP ↓) suppresses SCN neuronal firing to promote sleep onset. MT2 receptor activation phase-shifts the circadian clock for entrainment. The only chronobiotic agent that directly resets the master biological clock — not merely sedates.

MT1/MT2 Agonist

Master Physiological Antioxidant — Direct + Indirect Dual Pathway

Melatonin and its metabolites (AFMK, AMK) form a potent antioxidant cascade — each melatonin molecule neutralizes up to 10 ROS/RNS species via direct scavenging (versus glutathione’s single neutralization). Simultaneously, melatonin upregulates endogenous antioxidant enzymes: SOD, glutathione peroxidase (GPx), glutathione reductase, and catalase at the gene expression level — providing sustained oxidative defense beyond direct scavenging alone.

Antioxidant Cascade

Mitochondrial Protector — 100× Concentration in Mitochondrial Matrix

Melatonin is concentrated ~100× in the mitochondrial matrix vs the cytosol via oligopeptide transporter (PEPT1/2) active uptake. This unique subcellular targeting protects mtDNA from oxidative damage, maintains electron transport chain efficiency, reduces proton leak, preserves ATP synthesis under stress, and inhibits the mitochondrial permeability transition pore (mPTP) — preventing intrinsic apoptosis.

Mitochondrial-Targeted

Skin Anti-Aging & DNA Repair — Topical + Systemic Action

MT1 receptors expressed in epidermal keratinocytes and melanocytes mediate melatonin’s cutaneous benefits: upregulation of DNA repair enzymes, suppression of UVB-induced ROS, inhibition of collagen-degrading MMP-1/MMP-3, and reduction of UV-induced keratinocyte apoptosis. Topical melatonin (0.01–0.1%) provides overnight circadian-aligned skin repair. Amphiphilic nature enables both topical stratum corneum penetration and systemic blood-brain barrier crossing.

Cutaneous + Systemic

Applications

Sleep Formulations (0.5–10 mg)

Pharma-grade melatonin at physiological (0.5 mg) to therapeutic (5–10 mg) doses in capsules, tablets, gummies, liquid drops, and oral sprays for sleep onset, sleep maintenance, and circadian rhythm sleep disorders. Immediate release and sustained release profiles supported. OEM and private label formulations available with flexible MOQ starting at 1 kg.

Anti-Aging Night Creams & Serums (0.01–0.1%)

Topical melatonin at 0.01–0.1% in night creams, serums, and sleep masks for cutaneous MT1 receptor activation, overnight DNA repair, ROS scavenging, and circadian-aligned skin rejuvenation. Growing cosmeceutical segment — projected $150M+ globally by 2028. Pharma-grade purity ensures minimal impurity-related irritation risk for leave-on formulations.

Mitochondrial Health Supplements

Melatonin at 5–20 mg in targeted mitochondrial health formulations — leveraging the 100× mitochondrial matrix concentration gradient for mtDNA protection, electron transport chain support, and ATP synthesis preservation. Positioned for anti-aging, metabolic health, and cellular longevity supplement lines. Micronized grade recommended for enhanced absorption.

Jet Lag Formulations

Melatonin at 0.5–5 mg in rapid-dissolve tablets, oral sprays, and sublingual formats for jet lag prevention and treatment. Timed administration at destination bedtime accelerates circadian re-entrainment — clinical evidence supports 50% reduction in jet lag symptom severity with appropriately timed melatonin. Pharma-grade purity for premium travel health products.

Pediatric Sleep (Pharma)

Pharma-grade melatonin (≥99.5% USP/EP) at 0.5–10 mg for pediatric circadian rhythm sleep disorders, ADHD-related insomnia, autism spectrum disorder-associated sleep disturbance, and neurodevelopmental sleep conditions. Prescription-only positioning requiring pharmaceutical-grade raw material with Type II DMF support and full regulatory documentation.

Oncology Supportive Care

Pharma-grade melatonin at 10–20 mg/day as adjuvant to chemotherapy and radiotherapy — supported by clinical evidence for enhanced treatment tolerability, reduced chemotherapy-induced cytopenias and neurotoxicity, improved quality of life scores, and potential oncostatic effects (angiogenesis inhibition, immune surveillance enhancement). Type II DMF support for clinical and Rx development.

Frequently Asked Questions

Melatonin (N-Acetyl-5-methoxytryptamine, CAS 73-31-4) is an endogenous indoleamine hormone synthesized primarily in the pineal gland via the pathway tryptophan → 5-HTP → serotonin → N-acetylserotonin (NAS) → melatonin, with the rate-limiting step catalyzed by AANAT and the final step by HIOMT. As a circadian rhythm regulator, melatonin acts through MT1 and MT2 G-protein coupled receptors (G₁-protein → adenylyl cyclase ↓ → cAMP ↓ → CREB phosphorylation ↓) in the suprachiasmatic nucleus (SCN) — the brain’s master circadian pacemaker — to synchronize sleep-wake cycles with the environmental light-dark cycle. MT1 activation promotes sleep onset via SCN neuronal firing inhibition; MT2 activation phase-shifts the circadian clock for entrainment. As a master physiological antioxidant, melatonin operates through a dual pathway: (1) direct free radical scavenging — melatonin and its metabolites (AFMK, AMK) form a potent antioxidant cascade, each molecule neutralizing up to 10 ROS/RNS species versus glutathione’s single neutralization; (2) indirect antioxidant enzyme upregulation — melatonin stimulates gene expression of SOD, glutathione peroxidase (GPx), glutathione reductase, and catalase. Critically, melatonin is concentrated ~100× in the mitochondrial matrix vs cytosol — providing targeted protection at the cell’s primary ROS generation site. Its amphiphilic nature enables passive passage through all biological barriers including blood-brain and placental. Synthetic melatonin is chemically and structurally identical to endogenous human melatonin — the exact same molecule produced under pharmaceutical cGMP conditions. UPOR Biotech provides pharma grade (≥99.5% HPLC, USP/EP), nutraceutical/cosmetic grade (≥99%), and micronized grade.

Beyond circadian sleep regulation, melatonin provides five key systemic benefits: (1) Skin anti-aging — MT1 receptors are expressed in epidermal keratinocytes and melanocytes; melatonin upregulates DNA repair enzymes, suppresses UVB-induced ROS generation, inhibits collagen-degrading MMP-1/MMP-3, and reduces UV-induced keratinocyte apoptosis. Topical melatonin at 0.01–0.1% in night creams provides cutaneous circadian rhythm alignment and overnight skin repair. (2) Mitochondrial protection — melatonin is selectively concentrated ~100× in the mitochondrial matrix, where it protects mtDNA, maintains electron transport chain efficiency, reduces proton leak, preserves ATP synthesis under oxidative stress, and inhibits the mitochondrial permeability transition pore (mPTP) to prevent intrinsic apoptosis. (3) Oncostatic properties — melatonin inhibits tumor angiogenesis (VEGF ↓), enhances immune surveillance (NK cell activity, IL-2/IL-12 production), and potentiates chemotherapy efficacy while protecting normal tissues. (4) Metabolic health — regulation of insulin sensitivity, adipokine balance, and brown adipose tissue thermogenesis via MT1/MT2 receptor signaling in peripheral tissues. (5) Neuroprotection — blood-brain barrier penetration enables direct central nervous system antioxidant activity and protection against excitotoxicity relevant to neurodegenerative disease research and healthy brain aging. Topical + systemic melatonin represents a comprehensive approach: circadian-aligned skin repair from the outside, whole-body mitochondrial and antioxidant protection from the inside.

Dosage is strictly application-dependent: Sleep onset and circadian entrainment — 0.5–5 mg oral, 30–60 minutes before bedtime; the 0.5 mg physiological-dose range effectively shifts circadian phase without inducing supraphysiological plasma levels. Jet lag — 0.5–5 mg timed to destination bedtime, starting on travel day; clinical evidence shows 50% reduction in jet lag severity with appropriately timed dosing. Pediatric sleep disorders (pharma, Rx) — 0.5–10 mg under medical supervision for circadian rhythm disorders, ADHD-related insomnia, and neurodevelopmental conditions. Oncology supportive care — 10–20 mg/day as chemotherapy adjuvant under clinical protocol. Anti-aging topical — 0.01–0.1% in night creams and serums for localized cutaneous MT1 receptor activation and antioxidant activity. Available forms from UPOR Biotech: Immediate Release (standard powder for capsules, tablets, gummies, liquids), Sustained Release (hydrophilic matrix/polymer-based technologies delivering 6–8 hour plasma profiles mimicking endogenous pineal secretion), Micronized (D90 ≤10 µm for enhanced dissolution rate and oral absorption), and powder suitable for Transdermal/Topical formulation development. All three grade tiers — pharma (≥99.5%), nutraceutical/cosmetic (≥99%), and micronized — are available for each release profile. Sustained-release formulation represents the frontier of melatonin product innovation, transforming a short half-life (~40–60 minutes) molecule into a full-night chronobiotic delivery system.

Pharmaceutical-grade melatonin (≥99.5% HPLC, USP/EP monograph compliant) differs from nutraceutical/dietary supplement-grade (≥99% HPLC) in five material specifications: (1) Purity and related substances — pharma grade ≥99.5% with individual related substances ≤0.10% (any unspecified) / ≤0.15% (specified) and total impurities ≤0.5% per HPLC; supplement grade ≥99% with broader impurity allowance (individual ≤0.30%, total ≤1.0%). Key related substances monitored include N-acetyltryptamine, 5-methoxytryptamine, 5-methoxyindole-3-acetic acid, and oxidative degradation products — pharma-grade limits are 3–5× tighter. (2) Residual solvents — pharma grade provides full USP <467> / EP <5.4> / ICH Q3C Class 3 compliance with quantitative GC-HS residual solvent profile for every batch; supplement grade residual solvent testing may be limited or absent. (3) Elemental impurities — pharma grade Pb ≤2 ppm, As ≤1 ppm, Hg ≤1 ppm, Cd ≤1 ppm per USP <232>/ICH Q3D with full quantitative ICH Q3D Class 1/2A/2B/3 analysis; supplement grade typically provides total heavy metals ≤10 ppm as Pb only. (4) Microbial limits — both grades meet USP <61>/<62> and EP <2.6.12>/<2.6.13> (TAMC ≤100 CFU/g, TYMC ≤10 CFU/g, pathogens absent), but pharma grade provides endotoxin testing (USP <85>) and sterility data upon request. (5) Documentation and regulatory support — pharma grade includes USP/EP Monograph Compliance Certificate, Type II DMF with Letter of Authorization (upon signed CDA), full ICH stability data (2–8°C real-time 24-month + 25°C/60%RH accelerated 6-month), and complete lot traceability. For Rx pharmaceutical products (Circadin-class, pediatric formulations), clinical trial material, and premium cosmeceutical lines — pharma grade is the regulatory requirement. For dietary supplements, general nutraceutical formulations, and cosmetic night creams — the ≥99% grade provides excellent quality with cost-effectiveness.

Every shipment of melatonin includes: COA (HPLC purity ≥99.5% pharma or ≥99.0% nutraceutical/cosmetic, full related substances/impurity profile with individual impurity ≤0.10%, heavy metals ≤10 ppm with Pb ≤2 ppm / As ≤1 ppm / Hg ≤1 ppm / Cd ≤1 ppm, residual solvents per USP <467> / EP <5.4> / ICH Q3C with quantitative GC-HS profile, microbial panel per USP <61>/<62> and EP <2.6.12>/<2.6.13>), MSDS, HPLC Chromatogram (signed and dated), USP/EP Monograph Compliance Certificate (pharma grade), Type II DMF Letter of Authorization (pharma grade, upon signed Confidentiality Agreement), BSE/TSE-Free Statement, Non-GMO Statement, Allergen Statement, HALAL Certificate, KOSHER Certificate, ISO 22000 + HACCP, ISO 9001:2015, FDA Facility Registration, Stability Data (2–8°C real-time 24-month and 25°C/60%RH accelerated 6-month), and Complete Lot Traceability from raw material to finished product. Free sample available for qualified B2B buyers. MOQ: 1 kg. All documents provided in English. Additional endotoxin testing (USP <85>), sterility testing, and particle size distribution analysis (micronized grade) available upon request.