HYDROCODONE Chemical Properties

Melting point:

194-197°C

Boiling point:

440.69°C (rough estimate)

Density 

1.1613 (rough estimate)

refractive index 

1.5500 (estimate)

Flash point:

9℃

storage temp. 

Controlled Substance, -20°C Freezer

solubility 

Chloroform (Slightly), Ethyl Acetate (Slightly), Methanol (Slightly)

form 

Solid

pka

pKa 6.61(50% aq EtOH) (Uncertain)

color 

Prisms from EtOH

EPA Substance Registry System

Morphinan-6-one, 4,5-epoxy-3-methoxy-17-methyl-, (5.alpha.)- (125-29-1)

Safety Information

Hazard Codes 

F,T

Risk Statements 

11-23/24/25-39/23/24/25

Safety Statements 

16-36/37-45

RIDADR 

1544

WGK Germany 

1

HazardClass 

6.1(b)

PackingGroup 

III

HS Code 

2939110000

Hazardous Substances Data

125-29-1(Hazardous Substances Data)

Toxicity

LD50 s.c. in mice: 85.7 mg/kg (Eddy, Reid)

HYDROCODONE Usage And Synthesis

Chemical Properties

Beige Solid

Originator

Dicodid,Knoll,Belgium

Uses

Analgesic (narcotic); antitussive. Controlled substance (opiate).

Uses

Hydrocodone is a powerful anticough drug that is widely used for suppressing the cough reflex. It is widely used in effective commercial anticough drugs in combination with guaiphenesin (entuss), with homatropine (hycodan), with phenylpropanolamine (hycomine), phenyltoloxamine (tussionex), and pseudoephedrine and guaiphenesin (tussened).

Definition

ChEBI: A morphinane-like compound that is a semi-synthetic opioid synthesized from codeine.

Manufacturing Process

60 g of codeine about 94.5% (anhydrous codeine alkaloid basis) was dissolved in a solution made from 10 ml concentrated sulfuric acid and 390 ml water The mixture was refluxed for one hour with 25.0 g of 5% Pd on charcoal. The hot solution was immediately filtered and the catalyst was washed with 400 ml of dilute sulfuric acid of the same strength as was used in the rearrangement described above. To the combined cooled filtrate and wash, 750 ml if benzene was added, after which the mixture was cooled to 15°C, stirred, and made alkaline to pH 10 by addition of 80 ml of 40% NaOH. After shaking and separating the aqueous layer was extracted twice with 500 ml benzene. The combined benzene extracts are then extracted three times with 500 ml and twice with 400 ml portions of fresh 10% sodium bisulfite solution. Crude dihydrocodeinone was precipitated from bisulfite solution by eddition of 180 ml 40% NaOH at 15°C (to pH 10). The product was filtered, washed well and air-dried at room temperature. The melting point was about 184°C and yield about 35-38 g or 58-59%. The product was darken and the rest of Pd on charcoal and the original alkaloid were removed with column of Al2O3 (eluent - dry ethylene chloride) to give the dihyrocodeinone.

Therapeutic Function

Narcotic analgesic, Antitussive

General Description

Hydrocodone is the 3 methoxy version of hydromorphone.The loss of the 3-OH group yields a compound that is approximately4 to 5 times less potent than hydromorphone, thusabout equal to morphine. Unlike codeine, the agonist activityof hydrocodone does not require 3-O-demethylation, althoughit does occur via CYP2D6 representing 4.6% of totalclearance. The protected 3-position has better brain penetration,and the 7,8-dihydro-6-keto C ring contributes to the increasedbinding of the compound to the μ-receptor.
There are no pure hydrocodone products available on theU.S. market. All FDA-approved products containing hydrocodoneare combination products. Like codeine, hydrocodoneis marketed as an antitussive agent. It is availablecombined with the anticholinergic agent homatropineas a syrup and a tablet. The addition of the anticholinergicagent is to discourage abuse. It is also available in a delayedrelease suspension form (Tussionex). This formulation usesa sulfonated styrene divinylbenzene copolymer complexedwith hydromorphone and chlorpheniramine that acts as acation-exchange resin slowly releasing the drugs over a 12-hour period. Hydrocodone is also marketed in combinationwith acetaminophen (Vicodin, Lortab) or aspirin (LortabASA) for the treatment of pain. The dose of acetaminophenconsumed by the patient must be closely monitored, andprescriptions that allow for greater than 4 grams of acetaminophenper 24-hour period should not be dispensed.

Safety Profile

Poison by intravenous and subcutaneous routes. When heated to decomposition it emits toxic fumes of NOx.

HYDROCODONE(125-29-1)Related Product Information

• HYDROCODONE
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• HYDROCODONE FOR PEAK IDENTIFICATION - * NARC
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• HYDROCODONE-N-METHYL-D3,HYDROCODONE-D3,hydrocodone-d3solution,hydrocodone-n-methyl-d3solution
• HYDROCODONE-D6
• HYDROCODONE HYDROCHLORIDE
• HYDROMORPHONE-3BETA-D-GLUCURONIDE
• HYDROCODONE HYDROGEN TARTRATE 2.5-HYDRATE - * NARC
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• HYDROCODONE TARTRATE 2.5 HYDRATE
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• HYDROCODONE HYDROGEN TARTRATE 2.5-HYDRATEIMP. C (EP) AS PHOSPHATE HEMIHYDRATE:CODEINE PHOSPHATE HEMIHYDRATE[CONTROLLED SUBSTANCE]
• CODEINONE