Hydromorphone

Hydromorphone	Last updated: 10/09/2025
(Also known as: dihydromorphinone)

GENERAL INFORMATION

Description

A controlled veterinary drug, which is a morphine analogue usually used as the hydrochloride salt

Examples of veterinary uses

Used mainly as a sedative, restraining agent, analgesic or preanesthetic.

Examples of species treated

Dogs; Cats

Approval status

VMR 2013/2033 approval status (GB/UK)

Not approved

EU Regulatory approval status

Not approved

Chemical structure

Isomerism

Hydromorphone exhibits stereoisomerism due to its complex, multi-ring structure derived from morphine. It contains several chiral centres, which give rise to specific stereochemical configurations—notably the (4R,4aR,7aR,12bS) configuration in its active form. These chiral centres ensure that only one stereoisomer of hydromorphone is pharmacologically active and used in clinical settings, as other configurations would alter its interaction with opioid receptors. In addition to stereoisomerism, hydromorphone also displays polymorphism, meaning it can crystallise into different solid-state forms. Two known orthorhombic polymorphs, designated Form I and Form II, have been identified. While the molecular conformation remains largely consistent between them, subtle differences in hydrogen bonding patterns and torsion angles (especially around the N-methyl amine group) distinguish the two forms. These polymorphs can influence properties like solubility, stability, and bioavailability, which are critical in pharmaceutical formulation.

Chemical formula

C₁₇H₁₉NO₃

Canonical SMILES

CN1CCC23C4C1CC5=C2C(=C(C=C5)O)OC3C(=O)CC4

Isomeric SMILES

CN1CC[C@]23[C@@H]4[C@H]1CC5=C2C(=C(C=C5)O)O[C@H]3C(=O)CC4

International Chemical Identifier key (InChIKey)

WVLOADHCBXTIJK-YNHQPCIGSA-N

International Chemical Identifier (InChI)

InChI=1S/C17H19NO3/c1-18-7-6-17-10-3-5-13(20)16(17)21-15-12(19)4-2-9(14(15)17)8-11(10)18/h2,4,10-11,16,19H,3,5-8H2,1H3/t10-,11+,16-,17-/m0/s1

2D structure diagram/image available?

Yes

Cambridge Crystallographic Data Centre diagrams

Common Name	Relationship	Link
hydromorphone	-

General status

Veterinary substance type

Medicinal drug: analgesic

Substance groups

Opoid

Minimum active substance purity

Known relevant impurities

Substance origin

Synthetic

Mode of action

Acts by stimulating opiate receptors in CNS

Molecular targets

[Mu-type opioid receptor, Agonist], [Delta-type opioid receptor, Partial agonist], [Kappa-type opioid receptor, Agonist]

CAS RN

466-99-9

EC number

207-383-5

CIPAC number

US EPA chemical code

PubChem CID

Therapeutic Class

Analgesics: Opiods

ATCvet Code

QN02AA03; QN02AG04

Controlled Drug?

UK: Class A, Schedule 2; EU: UN61/72, Class I

Regulation 37/2010 MRL Classification

Molecular mass

285.34

PIN (Preferred Identification Name)

(4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro(3,2-e)isoquinoline-7-one

IUPAC name

(4R,4aR,7aR,12bS)-9-hydroxy-3-methyl-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro(3,2-e)isoquinoline-7-one

CAS name

4,5-epoxy-3-hydroxy-17-methylmorphinan-6-one

Forever chemical

Other status information

Relevant Environmental Water Quality Standards

Physical state

White to slightly yellow crystalline solid

Commercial

Property

Value

Availability status

Current

Introduction & key dates

1923, patented

Example manufacturers & suppliers of products using this active now or historically

Purdue Pharma, Canada

Example products using this active

Dilaudid

Formulation and application details

Typically supplied as a liquid injectable formulation, typically as hydromorphone hydrochloride.

Commercial production

Hydromorphone is synthesised through a semi-synthetic process starting from morphine, a naturally occurring alkaloid extracted from the opium poppy. The first step involves hydrogenation of morphine to produce dihydromorphine, which reduces the double bond in the morphinan ring system. This intermediate then undergoes Oppenauer oxidation, a reaction that selectively oxidises the hydroxyl group at the 6-position to a ketone, yielding hydromorphone. The compound is typically converted into its hydrochloride salt for pharmaceutical use, enhancing solubility and stability.

Impact on climate of production and use

Published GHG data is not available for most pharmaceuticals. However, according to industry, global averages suggest producing 1 kg of a typical active pharmaceutical ingredient can range from 10 to 100 kg CO₂e for small molecule drugs and potentially up to 1000 kg CO₂e for complex biologicals such as vaccines, depending on the drug type, its formulation, complexity of synthesis, solvent recovery, and energy sources used.

ENVIRONMENTAL FATE

Property

Value

Source; quality score; and other information

Interpretation

Solubility - In water at 20 °C (mg l⁻¹)

1931

at 25 °C

High

Solubility - In organic solvents at 20 °C (mg l⁻¹)

Melting point (°C)

266

Boiling point (°C)

100

Degradation point (°C)

Flashpoint (°C)

Octanol-water partition coefficient at pH 7, 20 °C

1.29 X 10⁰⁰

Calculated

Log P

0.11

Low

Fat solubility of residues

Solubility

Data type

Density (g ml⁻¹)

Dissociation constant pKa) at 25 °C

Vapour pressure at 20 °C (mPa)

Henry's law constant at 25 °C (Pa m³ mol⁻¹)

Volatilisation as max % of applied dose lost

From plant surface

From soil surface

Maximum UV-vis absorption L mol⁻¹ cm⁻¹

Surface tension (mN m⁻¹)

Refractive Index

Environmental release

Degradation

Property

Value

Source; quality score; and other information

Interpretation

Soil degradation (days) (aerobic)

DT₅₀ (typical)

DT₅₀ (lab at 20 °C)

DT₅₀ (field)

DT₉₀ (lab at 20 °C)

DT₉₀ (field)

Note

Manure DT₅₀ (days)

Aqueous photolysis DT₅₀ (days) at pH 7

Value

Note

Aqueous hydrolysis DT₅₀ (days) at 20 °C and pH 7

Value

Note

Water-sediment DT₅₀ (days)

Water phase only DT₅₀ (days)

Sediment phase only DT₅₀ (days)

Air degradation

As this parameter is not normally measured directly, a surrogate measure is used: ‘Photochemical oxidative DT₅₀’. Where data is available, this can be found in the Fate Indices section below.

Decay in stored produce DT₅₀

Soil adsorption and mobility

Property

Value

Source; quality score; and other information

Interpretation

Linear

K_d (mL g⁻¹)

Mobile

K_oc (mL g⁻¹)

Notes and range

Estimated

Freundlich

K_f (mL g⁻¹)

K_foc (mL g⁻¹)

¹/_n

Notes and range

pH sensitivity

Fate indices

Property

Value

Source; quality score; and other information

Interpretation

GUS leaching potential index

Bio-concentration factor

BCF (l kg⁻¹)

3.0

Low potential

CT₅₀ (days)

Known metabolites

None

ECOTOXICOLOGY

Terrestrial ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

Mammals - Short term dietary NOEL

(mg kg⁻¹)

(ppm diet)

Mammals - Chronic 21d NOAEL (mg kg⁻¹ bw d⁻¹)

Birds - Acute LD₅₀ (mg kg⁻¹)

Birds - Short term dietary (LC₅₀/LD₅₀)

Birds - Chronic 21d NOEL (mg kg⁻¹ bw d⁻¹)

Earthworms - Acute 14 day LC₅₀ (mg kg⁻¹)

Earthworms - Chronic NOEC, reproduction (mg kg⁻¹)

Soil micro-organisms

Collembola

Acute LC₅₀ (mg kg⁻¹)

Chronic NOEC (mg kg⁻¹)

Non-target plants

Vegetative vigour ER₅₀ (g ha⁻¹)

Seedling emergence ER₅₀ (g ha⁻¹)

Honeybees (Apis spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Unknown mode acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Chronic

Notes

Bumblebees (Bombus spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Mason bees (Osmia spp.)

Contact acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Oral acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg bee⁻¹)

Other bee species (1)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Other bee species (2)

Acute LD₅₀ (worst case from 24, 48 and 72 hour values - μg insect⁻¹)

Mode of exposure

Beneficial insects (Ladybirds)

Beneficial insects (Lacewings)

Beneficial insects (Parasitic wasps)

Beneficial insects (Predatory mites)

Beneficial insects (Ground beetles)

Aquatic ecotoxicology

Property

Value

Source; quality score; and other information

Interpretation

Temperate Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

Temperate Freshwater Fish - Chronic 21 day NOEC (mg l⁻¹)

Tropical Freshwater Fish - Acute 96 hour LC₅₀ (mg l⁻¹)

Temperate Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

Temperate Freshwater Aquatic invertebrates - Chronic 21 day NOEC (mg l⁻¹)

Tropical Freshwater Aquatic invertebrates - Acute 48 hour EC₅₀ (mg l⁻¹)

Aquatic crustaceans - Acute 96 hour LC₅₀ (mg l⁻¹)

Sediment dwelling organisms - Acute 96 hour LC₅₀ (mg l⁻¹)

Sediment dwelling organisms - Chronic 28 day NOEC, static, water (mg l⁻¹)

Sediment dwelling organisms - Chronic 28 day NOEC, sediment (mg kg⁻¹)

Aquatic Plants (free-floating, fonds growth, fresh) - 7 day (mg l⁻¹)

Aquatic plants (rooted, growth rate, fresh) - 14 day (mg l⁻¹)

Algae - Acute (growth rate, fresh; mg l⁻¹)

Algae - Chronic (growth rate, fresh; mg l⁻¹)

Mesocosm study data

NOEAEC mg l⁻¹

Marine bivalves

HUMAN HEALTH AND PROTECTION

General

Property

Value

Source; quality score; and other information

Interpretation

Threshold of Toxicological Concern (Cramer Class)

Mammals - Acute oral LD₅₀ (mg kg⁻¹)

Mammals - Dermal LD₅₀ (mg kg⁻¹ body weight)

Mammals - Inhalation LC₅₀ (mg l⁻¹)

Other Mammal toxicity endpoints

Subcutaneous LD₅₀ = 84.0 mg kg⁻¹

Mouse

Intravenous LD₅₀ = 104 mg kg⁻¹

Mouse

ADI - Acceptable Daily Intake (mg kg⁻¹ bw day⁻¹)

ARfD - Acute Reference Dose (mg kg⁻¹ bw day⁻¹)

AAOEL - Acute Acceptable Operator Exposure Level (mg kg⁻¹ bw day⁻¹)

AOEL - Acceptable Operator Exposure Level - Systemic (mg kg⁻¹ bw day⁻¹)

Dermal penetration studies (%)

Dangerous Substances Directive 76/464

Exposure Routes

Public

Occupational

Mammalian dose elimination route and rate

Metabolized in the liver as glucuronidated conjugate (major metabolite) and 6-hydroxy (minor metabolite) and excreted in the urine

Health issues

Specific human health issues

Carcinogen

Genotoxic

Endocrine disruptor

; ; ; ;

Reproduction / development effects

Acetyl cholinesterase inhibitor

Neurotoxicant

Respiratory tract irritant

Skin irritant

Skin sensitiser

Eye irritant

Phototoxicant

No data found

General human health issues

CNS toxicant - may cause respiratory depression, sedation and bradycardia
Skin & respiratory sensitiser

Handling issues

Property

Value and interpretation

General

When heated to decomposition it emits toxic fumes of nitroxides
Closed containers may explode from the heat of fire

CLP classification 2013

Helth: H317, H334; H336, H361

WHO Classification

Not listed (Not listed)

UN Number

Not regulated

Waste disposal & packaging

Shelf-life, storage, stability and reactivity

TRANSLATIONS

Language

Name

English

hydromorphone

French

German

Danish

Italian

Spanish

hydromorfona

Greek

Polish

Swedish

Hungarian

Dutch

Norwegian

Record last updated:	10/09/2025
Contact:	aeru@herts.ac.uk
Please cite as:	Lewis, K.A., Tzilivakis, J., Warner, D. and Green, A. (2016) An international database for pesticide risk assessments and management. Human and Ecological Risk Assessment: An International Journal, 22(4), 1050-1064. DOI: 10.1080/10807039.2015.1133242