Dextromethorphan

CAS Number 125-71-3
Molecular Formula C18H25NO
Molecular Weight 271.404 g/mol
InChI Key MKXZASYAUGDDCJ-NJAFHUGGSA-N
LogP 3.79
Synonyms
  • Dextromethorphan
  • (9alpha,13alpha,14alpha)-3-Methoxy-17-methylmorphinan
  • Morphinan, 3-methoxy-17-methyl-, (9alpha,13alpha,14alpha)-
  • 125-71-3
  • Nodex
  • Ba 2666
  • 3-Methoxy-17-methyl-9alpha,13alpha,14alpha-morphinan
  • (+)-Dextromethorphan
  • (9alpha,13alpha,14alpha)-3-Methoxy-17-methylmorphinan
  • 4-21-00-01367
  • Morphinan, 3-methoxy-17-methyl-, (9alpha,13alpha,14alpha)-
  • (+)-3-Methoxy-17-methylmorphinan
  • 9alpha,13alpha,14alpha-Morphinan, 3-methoxy-17-methyl-
  • D-3-methoxy-N-methylmorphinan
  • dextromethorphane
  • dextrometorfano
  • d-Methorphan
  • BRN 0088549
  • Dextromorphan
  • EINECS 204-752-2
  • delta-Methorphan
  • (+)-cis-1,3,4,9,10,10a-Hexahydro-6-methoxy-11-methyl-2H-10,4alpha-iminoethanophenanthren
  • (+)-3-Methoxy-N-methylmorphinon
  • Albutussin
  • Destrometerfano
  • Dextromethorfan
  • Dextromethorphanum
  • UNII-7355X3ROTS
  • 18046-32-7
  • 32062-10-5
  • 1469752-79-1

Applications:


Separation of NyQuil Active Ingredients on Primesep C



Primesep C separates the active ingredients in the over-the-counter cold medicine, NyQuil. Succinate and bromate co-elute early, but acetaminophen, pseudoephedrine, doxylamine, and dextromethorphan are baseline resolved. A combination of cation exchange, complex formation, and hydrophobic interactions separate this mixture with a mobile phase of water, acetonitrile (MeCN, ACN) and triethylamine (TEA) phosphate with UV detection at 205 nm.



Application Analytes:

Acetaminophen (Paracetamol)
Dextromethorphan
Doxylamine
Pseudoephedrine (PSE)

Separation and Retention of Dextromethorphan Bromide in Mixed-Mode HPLC: Buffer Concentration Effect
 
Dextromethorphan is used as a temporary cough suppressant in many medications. The elution time of dextromethorphan and bromide can be reversed in HPLC chromatography on a Primesep B2 reverse-phase (RP) column with embedded basic ion-pairing groups by only changing the concentration of buffer in a simple mobile phase of water and acetonitrile (MeCN, ACN). Buffer is trifluoroacetic acid (TFA). UV detection at 210nm. 

Application Analytes:

Bromide
Dextromethorphan

HPLC Separation of NyQuil Active Ingredients


NyQuil is a cough medication produced by Procter&Gamble. It consists of acetaminophen, pseudoephedrine, doxylamine and dextromethorphan. Most of the analytical HPLC methods include either use of ion-pairing reagent or a gradient elution. Mixed-mode chromatography allows to replace long gradient method with short isocratic method. All four compounds are well separated within 3-5 minutes. Methods can be optimized for analysis of other cough composition containing general cough suppressants and pain killers. Method is robust and being validated at several drug companies.



Application Analytes:

Acetaminophen (Paracetamol)
Dextromethorphan
Doxylamine
Pseudoephedrine (PSE)

HPLC Separation of Drugs
Mixed-mode chromatography allows to separate various hydrophobic and hydrophilic drugs in one HPLC method. Presence of at least two mechanism of retention allows adjust selectivity of separation by changing three parameters: amount of acetonitrile, buffer concentration and buffer pH. Seven common drugs are separated on a Primesep C trimodal HPLC column in gradient method. Method provides alternative selectivity to traditional reversed-phase chromatography. Operational range in which basic compounds are retained the most is from pH 3 to 5. At higher pH, longer retention can be achieved. Mixed-mode chromatography provides longer retention and better peak shapes for basic and acidic analytes. Method can be used in analysis of drugs and pharmaceuticals.

Application Analytes:

Dextromethorphan
Doxylamine
Norephedrine
Norphenylephrine
Pseudoephedrine (PSE)
Pyrilamine

Comparison of the Separation of Polar Drugs on Obelisc R and Zorbax SB-AQ


Common hydrophobic basic and hydrophilic basic drugs are separated by mixed-mode chromatography with greater selectivity and resolution than traditional reversed-phase column. Drugs are retained by combination of reversed-phase and cation-exchange mechanisms. Retention time is controlled by amount of acetonitrile, buffer concentration and buffer pH. Available detection techniques are based on buffer selection and include UV, Evaporative Light-Scattering Detector (ELSD), Corona (CAD), LC/MS, etc. This HPLC method can be adopted as general approach for analysis of drugs and pharmaceuticals.



Application Analytes:


Dextromethorphan
Doxylamine
Norephedrine
Norphenylephrine
Pseudoephedrine (PSE)
Pyrilamine

Separation of Drugs in Mixed-Mode HPLC


Obelisc R column can be successfully used for analysis of hydrophobic and hydrophilic basic and acidic drugs and corresponding counter-ions. This approach can be used for analysis of various cold and cough composition, pain killers, and other prescription and over-the-counter medications. Within pH 3-5, both cation- and anion mechanism are present on the column, along with hydrophobic interaction. Selectivity of this mixed-mode separation is controlled by the amount of acetonitrile, buffer concentration and buffer pH. Method is robust and reproducible, and can be used as a common HPLC method for analysis of drug molecules and compositions.



Application Analytes:

Acetaminophen (Paracetamol)
Dextromethorphan

HPLC Separation of Drugs in Tylenol Cold and Cough Remedies


Components of Tylenol Cold and Cough Remedy are separated on Obelisc R mixed-mode column. Method can be used to determine compounds in various cough and cold compositions. Neutral (acetaminophen), basic (chlorpheniramine, dextromethorphan and pseudoephedrine) and acidic (maleic acid/Maleate) components are analyzed with perfect peak shape and retention control. Method can be used in production, QC/QA and biological studies for quantitation of various components in pharmaceutical formulations (Advil, Tylenol, Dimetapp, Robitussin, NyQuil, etc)

Application Analytes:

Acetaminophen (Paracetamol)
Chlorpheniramine
Dextromethorphan
Maleate
Pseudoephedrine (PSE)

HPLC Separation of Drugs in Advil Allergy and Sinus


Ibuprofen is in a group of drugs called non-steroidal anti-inflammatory drugs (NSAIDs). Ibuprofen works by reducing hormones that cause inflammation and pain in the body.
Pseudoephedrine is a decongestant that shrinks blood vessels in the nasal passages. Dilated blood vessels can cause nasal congestion (stuffy nose).
The combination of chlorpheniramine, ibuprofen, and pseudoephedrine is used to treat sneezing, itching, watery eyes, runny nose, stuffy nose, sinus congestion, cough, and pain or fever caused by the common cold or flu in common over-the-counter medication (Advil, NyQuil, Tylenol, etc.)
Active ingredients of Advil Allergy and Sinus composition are separated by combination of reverse phase, cation-exchange and anion exchange mechanisms. Obelisc R mixed-mode column is used to separate pseudoephedrine (polar basic compound), chlorpheniramine (hydrophobic basic compound), ibuprofen (hydrophobic acidic compound) and maleic acid (counter-ion, hydrophilic acid compound). Method can be used for QC in production, impurity profiling and research and development. All compounds are well separated with high efficiency and good peak shape. Method uses ammonium formate buffer but other buffers can be used as well (ammonium acetate, sodium and ammonium phosphate) with corresponding detection technique - ELSD, LC/MS, and UV. Chlorpheniramine is an antihistamine that reduces the natural chemical histamine in the body. Histamine can produce symptoms of sneezing, itching, watery eyes, and runny nose.

Application Analytes:

Dextromethorphan
Ibuprofen
Maleate
Pseudoephedrine (PSE)

HPLC Analysis of Drugs in Saliva


The presence of three drugs, dextromethorphan, amitriptyline and trimipramine in saliva were analyzed by mixed-mode chromatography on a Primesep D reversed-phase anion-exchange column. No sample preparation is required as proteins from saliva are not retained at these conditions and elute in the void of the column due to cation-exclusion effect. Both column and proteins are positively charged at current conditions. Mobile phase consists of ACN-water-formic acid and is compatible with LC/MS detection technique. This general HPLC method can be used for analysis of hydrophobic basic drugs in biofluids.



Application Analytes:


Amitriptyline
Dextromethorphan

HPLC Analysis of Basic Drugs and Acidic Counter-Ions by Mixed-Mode Chromatography
The majority of drugs in the pharmaceutical industry are administered in salt form. The presence of two counter-ions very often necessitates the use of two methods. The nature of these counterparts in drugs can be an inorganic cation and organic acid, inorganic anion and organic base, and organic cation and organic anion. Furthermore, the properties of the molecules will result in a differing stoichiometry. The task of simultaneous quantitation of counter-ions can be achieved by using mixed-mode columns. The general approach for analysis is based on properties of corresponding counter-ions. Hydrophobic basic drugs, like dextromethorphan, verapamil, trimipramine, and corresponding acidic counter-ions (chloride, chlorate, bromide, bromate, perchlorate, maleate, fumarate,tartrate, succinate, phosphate, citrate, benzosulfonate, toleuensulfonate) can be separated and quantitated in the same run on reversed-phase anion-exchange column. Basic hydrophobic drugs are retained by the reversed-phase mechanism, and counter-ions are retained by the reversed-phase and anion-exchange mechanism. Some polar counter-ions are retained only by the anion-exchange mechanism. Retention time and selectivity of HPLC separation of drugs and counter-ions can be achieved by changing the amount of acetonitrile and the amount of ions in the mobile phase. The detection technique depends on the properties of the counter-ions. In case of low or no UV activity, ELSD can be employed if the counter-ion forms a non-volatile salt with the mobile phase additive (ammonium formate). This HPLC method can be used for simultaneous quantitation of other basic drugs and counter-ions. The presence of two mechanisms of retention allows control over retention times of drug and counter-ion independently, and even allows a change of order of elution when necessary.

Application Analytes:

Benzenesulfonic Acid
Bromide
Chlorate
Chloride
Citric Acid
Dextromethorphan
Fumaric Acid
Maleic Acid
Organic Acids
Perchlorate
Phosphoric Acid
Pyrilamine
Succinic Acid
Tartaric Acid
Verapamil
p-Toluenesulfonic Acid (PTSA)

Analysis of Dextromethorphan-Based Composition
 

Condition

Column Primesep C, 4.6x150 mm, 5 µm, 100A
Mobile Phase MeCN/H2O
Buffer TEAPh
Flow Rate 1.0 ml/min
Detection UV, 210 nm
 

Description

Class of Compounds Drug, Preservatives,  Base, Hydrophobic, Ionizable
Analyzing Compounds Dextromethorphan, Bromide, Methyl Paraben, Propyl Paraben
 

Application Analytes:

Bromide
Dextromethorphan
Methylparaben
Propylparaben

Analysis of Dextromethorphan-Based Drug composition. Effect on buffer pH
Dextromethorphan is one of the common cough suppressants used in many drug composition. It is in tablets and syrups as an antitussive drug. Composition often has preservatives like parabens. Dextromethorphan is a hydrophobic, basic drug which is used as a bromide salt in drug compositions. Dextromethorphan and two parabens (methyl paraben and propyl paraben) were separated on Primesep C reversed-phase cation-exchange column. Several impurities were observed and are well separated from the main components of the drug composition. Method can be used for various formulations in QC and production environment.  

Condition

Column Primesep C, 4.6x150 mm, 5 µm, 100A
Mobile Phase MeCN/H2O - 35/65%
Buffer TEAPh
Flow Rate 1.0 ml/min
Detection UV, 210 nm
 

Description

Class of Compounds Drug, Preservatives,  Base, Hydrophobic, Ionizable
Analyzing Compounds Dextromethorphan, Bromide, Methyl Paraben, Propyl Paraben
 

Application Analytes:

Bromide
Dextromethorphan
Methylparaben
Propylparaben