Acetaminophen
Acetaminophen is an analgesic and an antipyretic, but the exact mechanism of the drug action is not fully understood. It appears to relieve pain by raising the pain threshold so that a greater amount of pain is necessary before it can be felt. Its antipyretic action results from its effect on the heat-regulating centers of the brain. Chemically, acetaminophen is p-hydroxy acetanilide, it has a molecular weight of 151.16 and elemental analysis shows it contains 67.38% carbon, 9.43% hydrogen, 5.24% nitrogen and 17.95% oxygen. Acetaminophen is prescribed for arthritis but is not an anti-inflammatory, it is mainly used to help reduce temperature and as a mild analgesic. Acetaminophen tablets have been successfully analyzed using reversed phase (C18) columns 20-25 cm long 3-4.6 mm in diameter using a strongly polar, water-methanol-acetonitrile mixture with a tetramethylammonium hydroxide buffer as the mobile phase. By employing a C18 stationary phase strong dispersive interactions are exploited in the stationary phase whereas predominantly polar interactions are active in the mobile phase. Separations can be easily obtained in 5 to 10 minutes
Author: RPW Scott
Book:Principles and Practice of Chromatography
Section:Principles Applications Liquid-Chromatography
(adjusted to pH 7 with 85% phosphoric acid)60% acetonitrile and 15% methanol
Flow-Rate
2 ml/min.
Detector
UV adsorption at 215 nm
Sample Volume
100ml
An example of
the use of native silica is in the analysis of Darvocet® and its generic
equivalent formulation. The separation obtained is shown in figure 44.
Darvocet® is an acetaminophen product of which acetaminophen itself is the
active ingredient together with other weakly polar substances present.
Consequently, the mixture lends itself to separation on silica gel. The
analysis was completed in less than 4 minutes using a short column 3.3 cm long
and 4.6 mm in diameter. The silica packing had a particle size of 3 m providing a maximum efficiency of about
5,500 theoretical plates.
Courtesy of Supelco Inc.
Figure 44
The Analysis of Acetaminophen Formulations
Principles Applications Liquid-Chromatography
Author: RPW Scott
Book:Principles and Practice of Chromatography
Section:Principles Selectivity Polar
An interesting
example of polar selectivity by hydroxyl groups on the surface of native
silica is shown by the analysis of Darvocet® and its generic equivalent in
figure 15.
Courtesy of Supelco
Inc.
Figure 15 The
Analysis of Acetaminophen Formulations
Darvocet® is
an acetaminophen product in which it is the active ingredient. Other substances are present which also contain
polar groups and thus, the sample lends itself to separation on the polar
stationary phase, silica gel. The analysis was completed in less than 4 minutes
using a short column 3.3 cm long and 4.6 mm in diameter packed with silica
(particle size of 3 m). The column
appears to be significantly overloaded, but the impurities are
Principles Selectivity Polar
Author: RPW Scott
Book:Liquid Chromatography
Section:HPLC Applications
was shown to be present in the generic formulation that was not in
the Darvocet®. The mobile phase was 98.5% dichloromethane with 1.5% v/v of
methanol containing 3.3% ammonium hydroxide. The ammoniacal methanol deactivated
the silica gel but the interaction of the solutes with the stationary phase
would still be polar in nature. In contrast solute interactions with the
methylene dichloride would be exclusively dispersive.
Courtesy of Supelco Inc.
Figure 59.
The Analysis of Acetaminophen Formulations
Ion
chromatography can be used in a number of novel ways and employing the
appropriate conditions can even be used to separate mixtures where the
components are not ionic or do not normally produce interactive ions in
aqueous solution. An example of this type of separation is the analysis of
saccharide mixtures using ion exchange interactions. An illustration of such a
separation is given in figure 60. The saccharides are reacted with a borate
with which
HPLC Applications
Author: RPW Scott
Book:Liquid Chromatography
Section:HPLC Applications
the stationary phase would become almost
exclusively dispersive. This is an example where a complex phase system was
necessary because there was limited column efficiency available. It is likely
that a column with intrinsically more efficiency might achieve the separation
with a much simpler solvent system and a more straightforward solvent program.
An example of
the use of native silica is given by for the analysis of Darvocet® and its
generic equivalent formulation. Darvocet® is an acetaminophen product in which
the active ingredient (and other material in the medicine) are weakly polar
and, consequently, lend themselves to separation on a strongly polar stationary
phase such as silica gel. The analysis is depicted in figure 59. The analysis
is completed in less than 4 minutes using a short column 3.3 cm long and 4.6 mm
in diameter. The silica packing had a particle size of 3 m providing a maximum efficiency of about
5,500 theoretical plates
HPLC Applications