Identification

Name
Patent Blue
Accession Number
DB13967
Type
Small Molecule
Groups
Approved
Description

Patent blue is aniline dye and it is one of the most common dyes used.[1] It is a sodium or calcium salt of diethylammonium hydroxide inner salt.[2] It has the chemical designation of (4-(alpha-(p-(diethylamino)phenyl)-2,4-disulfobenzylidene)-2,5-cyclohexadiene-1-ylidene)diethylammonium hydroxide. Patent blue was developed by Guerbet and approved by Health Canada on December 31, 1979.[5] The isomer isosulphan is used in the United States for the same indications than patent blue.[2]

Structure
Thumb
Synonyms
  • patent blue violet
Product Ingredients
IngredientUNIICASInChI Key
Patent Blue V calcium8QE473DV1Z3536-49-0RTMBGDBBDQKNNZ-UHFFFAOYSA-L
Patent Blue V sodium9ZL680Q9Z520262-76-4PMLFOMWMYRKZRF-UHFFFAOYSA-M
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Patent Blue Sodium InjectionSolution50 mgIntravenous; SubcutaneousGuerbet1979-12-31Not applicableCanada
Categories
UNII
D4RJJ6R97N
CAS number
25305-77-5
Weight
Average: 561.69
Monoisotopic: 561.172370179
Chemical Formula
C27H33N2O7S2
InChI Key
DHAHKSQXIXFZJB-UHFFFAOYSA-O
InChI
InChI=1S/C27H32N2O7S2/c1-5-28(6-2)21-13-9-19(10-14-21)27(20-11-15-22(16-12-20)29(7-3)8-4)23-17-24(30)26(38(34,35)36)18-25(23)37(31,32)33/h9-18H,5-8H2,1-4H3,(H2-,30,31,32,33,34,35,36)/p+1
IUPAC Name
4-{[4-(diethylamino)phenyl](5-hydroxy-2,4-disulfophenyl)methylidene}-N,N-diethylcyclohexa-2,5-dien-1-iminium
SMILES
CCN(CC)C1=CC=C(C=C1)C(=C1C=CC(C=C1)=[N+](CC)CC)C1=C(C=C(C(O)=C1)S(O)(=O)=O)S(O)(=O)=O

Pharmacology

Indication

Patent blue is used for marking lymphatic vessels and arterial territories as well as for sentinel lymph node prior to biopsy in patients with operable breast cancer and clinically negative lymph nodes in combination with a radiotracer.[3]

Patent blue is also used in the textile, paper, agriculture and cosmetic industry.[2]

Pharmacodynamics

Administration of patent blue has been reported to cause hypersensitivity reactions in approximately 1% of the patients. It also presents a localized blue coloration which has made patent blue a sensitive and specific option for the detection of micrometastatic cancer in lymph nodes.[4]

Mechanism of action

The specific binding of patent blue allows it to freely travel in the breast lymphatics and allows staging with a less invasive alternative. Patent blue will form a complex with albumin which will be picked up by regional afferent lymphatics to identify sentinel lymph nodes.[3] A sentinel lymph node is the first lymph node in a chain or group of lymph nodes that cancer is most likely to spread to. The determination of the sentinel lymph node allows the physician to stage cancer by observing if cancer has spread to the near lymph nodes.[6]

TargetActionsOrganism
ASerum albumin
binder
Human
Absorption

Patent blue is selectively absorbed in the lymphatics.[2] When administered orally, patent blue has a very low absorption and limited systemic availability.[8]

Volume of distribution

This pharmacokinetic parameter has not been studied.

Protein binding

Patent blue gets specifically bound to albumin which allows it to travel through the breast lymphatics.[3]

Metabolism

In vitro studies have shown that patent blue is not metabolized.[8]

Route of elimination

Patent blue is excreted into the urine and bile.[2]The excretion is more significant in the urine which after the administration of patent blue intravenously can even change to a blue coloration.[7] When administered orally, patent blue is excreted unchanged in feces.[8]

Half life

The elimination half-life is of about 24-48 hours.[7]

Clearance

This pharmacokinetic property has nos been fully studied.

Toxicity

Overdose studies have not been performed but major cases of hypersensitivity have been reported.[7]

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AcebutololThe risk or severity of hypersensitivity reaction can be increased when Patent Blue is combined with Acebutolol.
AcetaminophenAcetaminophen may decrease the excretion rate of Patent Blue which could result in a higher serum level.
Acetylsalicylic acidAcetylsalicylic acid may decrease the excretion rate of Patent Blue which could result in a higher serum level.
AdenosineThe therapeutic efficacy of Adenosine can be decreased when used in combination with Patent Blue.
AdrenaloneThe therapeutic efficacy of Adrenalone can be decreased when used in combination with Patent Blue.
AgmatineThe therapeutic efficacy of Agmatine can be decreased when used in combination with Patent Blue.
AlprazolamAlprazolam may decrease the excretion rate of Patent Blue which could result in a higher serum level.
AlprenololThe therapeutic efficacy of Alprenolol can be decreased when used in combination with Patent Blue.
AmbrisentanThe therapeutic efficacy of Ambrisentan can be decreased when used in combination with Patent Blue.
AmilorideAmiloride may increase the excretion rate of Patent Blue which could result in a lower serum level and potentially a reduction in efficacy.
Food Interactions
Not Available

References

General References
  1. Iqbal FM, Basit A, Salem F, Vidya R: Feeling blue, going green and finding other attractive alternatives: a case of biphasic anaphylaxis to patent blue and a literature review of alternative sentinel node localisation methods. BMJ Case Rep. 2015 Dec 15;2015. pii: bcr-2015-213107. doi: 10.1136/bcr-2015-213107. [PubMed:26670899]
  2. Tripathy S, Nair PV: Adverse drug reaction, patent blue V dye and anaesthesia. Indian J Anaesth. 2012 Nov;56(6):563-6. doi: 10.4103/0019-5049.104576. [PubMed:23325942]
  3. Gumus M, Gumus H, Jones SE, Jones PA, Sever AR, Weeks J: How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye. Breast Care (Basel). 2013 Jun;8(3):199-202. doi: 10.1159/000352092. [PubMed:24415970]
  4. Joshi M, Hart M, Ahmed F, McPherson S: Adverse reaction; patent blue turning patient blue. BMJ Case Rep. 2012 Nov 30;2012. pii: bcr-2012-007339. doi: 10.1136/bcr-2012-007339. [PubMed:23203181]
  5. Health Canada [Link]
  6. Canadian Cancer Society [Link]
  7. Patent blue V monograph [Link]
  8. European Food Safety Authority [Link]
External Links
ChemSpider
69520
ChEBI
59601
Wikipedia
Patent_Blue_V
AHFS Codes
  • 36:89.00* — Other Diagnostics
FDA label
Download (343 KB)
MSDS
Download (47.5 KB)

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
FormRouteStrength
SolutionIntravenous; Subcutaneous50 mg
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)200 ºC'MSDS'
boiling point (°C)Decomposes'MSDS'
water solubilitySoluble'MSDS'
logP-1.82'MSDS'
pKa7.63Nollet L. and Toldra F. Handbook of food analysis. (2015)
Predicted Properties
PropertyValueSource
Water Solubility0.00268 mg/mLALOGPS
logP-0.5ALOGPS
logP2.4ChemAxon
logS-5.4ALOGPS
pKa (Strongest Acidic)-2.6ChemAxon
pKa (Strongest Basic)5.33ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count8ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area135.22 Å2ChemAxon
Rotatable Bond Count9ChemAxon
Refractivity173.8 m3·mol-1ChemAxon
Polarizability59.14 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
Not Available

Taxonomy

Classification
Not classified

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 Da
References
  1. Gumus M, Gumus H, Jones SE, Jones PA, Sever AR, Weeks J: How long will I be blue? Prolonged skin staining following sentinel lymph node biopsy using intradermal patent blue dye. Breast Care (Basel). 2013 Jun;8(3):199-202. doi: 10.1159/000352092. [PubMed:24415970]

Drug created on January 17, 2018 14:10 / Updated on September 17, 2018 21:06