Type of mill Product Maximum Cleaning operation Price kF

specific feed rate

surface
(m2 /g)
Pane cake 1.77 10 kg/h Easy Easy 200
mill Mechanically
simple, little
or no
maintenance
Oval ring mill 0.596 30 kg/h Easy Easy 200
Mechanically
simple, little
or no
maintenance
Fluid 1.12 7 kg/h for N Difficult Difficult 1000
bed+selector less than 7000 Mechanically
rpm 2.5 kg/h complex,
for N greater requires
than 7000 regular
rpm maintenance
Pin mill 0.41 25 kg/h Less easy Less easy 250
(100mm) Requires
regular
maintenance
Fixed 0.52 25 kg/h for Less easy Less easy 250
hammer mill dgridz greater Requires
than or equal regular
to 0.3 mm 7 maintenance
kg/h for less
than
dgridb0.3 mm
Pin 1.22 75 kg/h Difficult Requires 500
mill+selector regular
maintenance
Advances in pharmacognosy

Advance grinding techniques:

The table below shows some of modern grinding techniques in form of table: it shows that the
pancake mill is preferred for ultra-fine grinding as it is simple to use, can treat high feed rates
and is easy to clean. For fine or coarse grinding the oval ring mill and the pin mill are
comparable. The MS20 can be useful if tight size distributions are required.
Advanced drying techniques:
In recent years, a variety of technological advances have been made in the area of industrial
drying of food and medicinal plants, including the development of techniques, equipment, and
quality.
Microwave drying, heat pump drying, Refractance window drying, fluidized bed drying and
radio frequency drying are among the novel methods for improving the efficiency and efficacy of
drying, thus reducing energy use and preserving product quality simultaneously.

Heat Pump Drying (HPD)

In the early 1950s, experimentation with heat pumps was conducted to dry clothes; the concept
was mechanically feasible, but wasn’t appealing because of low fuel prices. As fuel prices rose,
heat pumps became popular. In conventional dryers, high-quality energy (such as electricity or
fuel) would be used to heat the air and a stream of moist, hot air would be expelled at the
exhaust. This represented a significant amount of low-grade energy that was being lost during
the process. In order to reduce this loss, heat pumps were introduced to the systems to recover
the latent heat of evaporation of water lost in the exhaust from the dryer. With the heat pump
evaporator placed in the exhaust stream of the dryer, the air is cooled (to recover the sensible
heat component) and then dehumidified (to recover latent heat) by the refrigerant. The heat
added to the refrigerant is then transferred to the air stream entering the dryer at the condenser of
the heat pump, thus raising its temperature. The added benefit of dehumidifying the drying air is
also realized
when
the air
leaves
the dryer
and is

recirculated, increasing its capacity to achieve better drying.

Microwave Drying (MD)

During Microwave Drying, electrical energy is used at frequencies between 300 MHz and 300
GHz, with 2,450 MHz being the most commonly used frequency. In a microwave oven,
alternating current is stepped up from 60 Hz to 2,450 MHz using alternating current from a
domestic power line. This is accomplished by utilizing a device known as the magnetron. The
use of microwave energy for drying has shown to be relatively energy-efficient. Microwaves are
an attractive source of thermal energy, due to their volumetric heating and short processing
times. It generates rapid volumetric heating of materials in food products by altering their
electromagnetic fields to interact with primarily water molecules and ions. However, as
microwaves alone cannot complete the drying process, it is recommended to combine other
techniques, such as forced air or vacuum, to further enhance the efficiency of the microwave.
Drying of food by the use of Intermittent Microwave Convection Drying (IMCD) being an
advanced technique improves energy efficiency and food quality at the same time.
Refractance Window Dryer (RWD)

During the Refractance window drying process, circulating water at 95-97°C transfers thermal

energy to the materials being dried. An evenly distributed plastic conveyer belt passes over a hot
water trough as the pureed products are distributed. When the dried product reaches the cold-
water section, it hardens, making it easier to separate from the belt using a scraper. Ideally, this
technology is suitable for products with a distinct aroma and vibrant colour that are pureed or
semi-solid. Using this method, fruits, vegetables and herbs with high moisture content can be
dried in 3-5 minutes, while retaining their colour, vitamins and antioxidants. The RW drying
method has been found to be a viable and low-cost method for producing edible films with
adequate technological characteristics and high nutritional value. The dehydrated products can be
consumed directly or used in the development of food products.

Radio-frequency (RF) Drying

Researchers are becoming more interested in RF drying, owing to the increased penetration
depth, homogeneity of heating and control of product temperature. The method is also known as
dielectric heating. The RF method of heating food is faster and more efficient, because internal
heat is generated in the treated food, due to ionic conductance and dipole rotation of molecules.
Hence, food quality could be preserved by evaporating only the water and heating it only
minimally. RF heaters are used frequently in the final stages of drying to
improve energy efficiency and product quality. Conventional hot-air drying methods for solid or
semi-solid foods are inefficient at removing moisture during the falling rate period. Moreover,
traditional drying involves adding heat from the inside to the outside of the food, which results in
cracks and hard shells in the final product. Aside from its selective and volumetric heating
capabilities, RF drying has two major advantages over hot-air drying. While RF drying is quite
useful in the food industry, where high throughput is needed, the operating costs of such a
process are not usually economically viable .

Advanced extraction techniques:

Microwave-assisted extraction (MAE)
Microwaves are part of the electromagnetic spectrum of light with a range of 300 MHz to
300 GHz, and wavelengths of these waves range from 1 cm−1 to 1 m−1.These waves are made up
of two perpendicular oscillating fields which are used as energy and information carriers.
eduction, volume generation due to heat, equipment size reduction, because of the higher process
rates, and thus increase in productivity, through better usage of the same equipment process
volume. MAE is a feasible green solvent extraction procedure as it uses water or alcohol at

elevated temperature and controlled pressure conditions

Ultrasound-assisted extraction (UAE) or sonication extraction

This extraction method involves using ultrasound with frequencies ranging from 20 to 2000
KHz; this increases the permeability of cell walls and produce cavitation. Although the process is
helpful in some cases, its large-scale application is limited due to its high cost. The most
noticeable disadvantage of the procedure is the occasional but known deleterious effect of
ultrasound energy on the active components of the medicinal plants through the formation of free
radicals and consequently undesirable changes on the drug molecules . The schematic
representation of the equipment is given below
Pressurized liquid extraction (PLE) or accelerated solvent extraction (ASE)
Pressurized liquid extraction (PLE) also known as pressurized fluid extraction (PFE), accelerated
solvent extraction (ASE), and pressurized solvent extraction (PSE), or as enhanced solvent
extraction system (ESE).
Dionex Corporation introduced PLE in 1995 as an alternative to maceration, percolation,
sonication, Soxhlet extraction, etc. It is an automated technique for extracting solid samples with
liquid solvents (either aqueous or organic, single or mixtures) above their boiling point, combine

high
pressures (4–12 MPa) and moderate to high temperatures (50–300°C). When water is the
extraction solvent, different terms are used to define the method, that includes hot water
extraction (HWE), subcritical water extraction (SWE), high-temperature water extraction
(HTWE), hot water extract pressurized (PHWE), liquid water extraction or superheated water
extraction Sample size, solvent, pressure, temperature, pH, flow rate, extraction time are the
standard parameters influencing the PLE process, with temperature and solvent type being the
most significant ones In this process, for a short period of time (5–10 min), a cartridge in which
the ample has been placed is filled with an extracting solvent and used to statically extract the
sample under elevated temperature and pressure. To purge the sample extract from the extraction
cell into a collector flask pressurized gas is used.

Supercritical fluid extraction (SFE)

SFE is used for separating components from the matrix with the application of supercritical
fluids as the extracting solvent
The SFE extraction procedure possesses distinct advantages:
1. the extraction of constituents is carried out at a low temperature, strictly avoiding damage
from heat and some organic solvents. SFE offers gentle treatment for heat-sensitive
material;
2. fragrances and aroma remain unchanged;
3. CO2 is an inexpensive solvent;
4. No solvent residues are left behind;
5. possibility of direct coupling with analytical chromatographic techniques such as gas
chromatography (GC) or supercritical fluid chromatography (SFC);
1. environmentally friendly extraction procedure. CO2 as the solvent does not cause
environmental problems and is physiologically harmless, germicidal, and non-flammable.
Some specific disadvantages of this method are:
1. high investment cost;
2. the use of high pressures leads to capital costs for the plant, and operating costs may also
be high, so the number of commercial processes utilizing supercritical fluid extraction is
relatively small, due mainly to the existence of more economical methods;
3. high polar substances (sugars, amino acids, inorganic salts, proteins, etc.) are soluble;
4. phase equilibrium of the solvent/solute system is complex and making design of
extraction conditions is difficult.
SFE finds extensive application in extracting pesticides, environmental samples, foods and
fragrances, essential oils, polymers, and natural products. Conde-Hernández and collaborators
extracted the essential oil of rosemary (Rosmarinus officinalis) by S-CO2 extraction, hydro
distillation and steam distillation. They found that both yields of essential oil and antioxidant
activity of SFC extract were higher than those from the other two methods

Pulsed electric field (PEF) extraction

Pulsed electric field extraction is a technique based on the exposure of vegetable matrix to an
electrical potential. A transformer generates an electric pulse, increasing voltages from 140 or
220 V to 1000 V, or even greater than that (25000 V). A capacitor transforms this high voltage in
a closed chamber with metallic electrodes. The general scheme of PEF equipment is presented in
figure.
This “cold” extraction assisted
by PEF prevent the
degradation of the cell and the
extraction of components from
the intracellular
vacuoles. It considerably increases the yield and decreases the time because it can increase mass
transfer by destroying membrane structures during the extraction process.
Specific energy input, treatment temperature and field strength are considered among parameters
that can influence the treatment efficacy of the PEF extraction. It is known as a non-thermal
method which reduces the decomposition of the thermolabile components

Enzyme-assisted extraction (EAE)

The EAE is an enzymatic pre-treatment that is carried out by the addition of specific hydrolyzing
enzymes during the extraction step. In the cell membrane and cell wall structure, micelles are
formed by macromolecules such as polysaccharides and protein. The coagulation and
denaturation of proteins at high temperatures during extraction are the main barriers to
extracting natural products. EAE enhance the extraction efficiency due to the hydrolytic action
of the enzymes on the components of the cell wall and membrane and the macromolecules inside
the cell, which facilitate the release of the natural products. Cellulose, α-amylase, and pectinase
are hydrolyzing enzymes usually employed in EAE. This procedure is suitable for extracting
various bioactive substances from plant matrices, but after filtration the obtained fraction is rich
in small water-soluble molecules that include polyphenols and flavonoids
 Turbo-
distillation
extraction or turbo-extraction (turbolysis)
Turbo-distillation was patented in 1983 by Martel, and has been used in several companies as an
industrial purpose for extracting EOs from hard matrixes (such as wood, bark, and seeds) The
extraction process is similar to hydrodistillation with slight modifications. The turbo-extraction
or turbolysis is based on extraction with stirring and simultaneous reduction of particle size. Due
to of high shearing force, cells disruption leads to rapid dissolution of the active constituents. It
results in an extraction time of the order of minutes and the plant content is almost completely
depleted. Compare to hydrodistillation, turbo-distillation minimize extraction time and energy
consumption and prevents the degradation of volatile constituents

Counter-current extraction (CCE)

In this procedure, the wet raw material is pulverized to produce a fine slurry. The target material
is moved in one direction (usually as a fine slurry) within a cylindrical extractor where it comes
in contact with extracting solvent. Further, the starting material moves making more
concentrated extract. Thus, complete extraction is possible when the amounts of material and the
flow rate of solvent are optimized the complete extraction is possible. The process is extremely
efficient, takes little time and poses no danger when high temperature is applied. Lastly, the
extracts come out sufficiently concentrated at one end of the extractor, while the residue falls on
the other end.This extraction procedure has great advantages:
1. compared to other methods such as maceration, decoction, percolation a unit amount of
the plant material cab be extracted with a much smaller volume of solvent;
2. CCE is usually performed at room temperature, which avoids the
thermolabile constituents from being exposed to heat which is used in most other
techniques;
 3. Since the drug is pulverized under wet conditions, the heat generated during
comminution is neutralized by water. This once more avoids the thermal degradation of
components from heat exposure;
4. Compare to continuous hot extraction, CCE is rated to be more efficient and effective.

Solid-phase extraction (SPE)

Solid-phase extraction (SPE) is a sample preparation technology using chromatographic packing
material, solid particle, commonly found in a cartridge type device, to chemically separate the
different components. Samples are almost constantly in the liquid state (although special
applications can be run with some samples in the gas phase). In this method, the dissolved or
suspended compounds in a liquid mixture are separated from other compounds depending on
their physical and chemical properties. The technically correct name for this technology is
“Liquid–Solid Phase Extraction”, since the chromatographic particles are solid and the sample is
in the liquid state.SPE has many benefits, but four significant benefits deserve special
attention:simplification of complex sample matrix along with compound purification;reduce ion
suppression or enhancement in MS applications;capability to fractionate sample matrix to
analyze compounds by class;trace concentration (enrichment) of very low-level compounds.
This rapid, economical and sensitive technique uses different types of cartridges and disks, with
various sorbents, where the solute molecules are preferentially attached over the stationary
phase.

High-voltage-assisted extraction
The principle of this equipment is similar to PEF, with the difference that electrical discharge is
made through a small point. For this, a needle electrode is used from which the release is made in
a plate ground electrode.
These methods are known as greener methods, are often better than conventional ones in terms
of high yields, high selectivity, lower solvent consumption and shorter extraction time. They are
also found to be environmentally ecofriendly since energy, and organic solvent consumption are
reduced. The combination of extraction methods to obtain high purity extracts or high overall
yields are described in the literature. Its main advantage is the operability in continuous mode,
which is very important from an industrial and economic point of view.

Phytonics process
A new solvent-based on hydrofluorocarbon-134a and a new technology to optimize its
remarkable properties in the extraction of plant material offer significant environmental
advantages and health and safety benefits over traditional processes to produce advanced quality
natural fragrant oil, flavors and biological extracts.
The technology known as “phytonics process” was developed and patented by Advanced
Phytonics Limited (Manchester, UK). Fragrant components of EOs and biological or
phytopharmacological extracts that can be used straightly without additional chemical or
physical treatment are the products frequently extracted by this process. The properties of the
new generation of fluorocarbon solvents have been applied to the extraction of plant material.
The core of the solvent is 1,1,2,2-tetrafluoroethane, better known as hydrofluorocarbon-134a
(HFC-134a) with a boiling point of – 25°C; a vapor pressure of 5.6 bar at ambient temperature. It
is flammable and non-toxic. This product was developed s a replacement for chlorofluorocarbons
and more importantly, it does not deplete the ozone layer. By most standards this is a poor
solvent that is unable to break up (dissolve) plant waste
. The process is advantageous because the solvents can be customized: by using modified
solvents with HFC-134a, the process can be made highly selective in extracting a specific class
of phytoconstituents. Likewise, to withdraw a broader spectrum of constituents other modified
solvents can be employed. The biological products obtained by this process contain extremely
low residual solvent. Residuals are constantly below the levels of detection and are fewer than 20
parts per billion. Therefore, selected solvents have minimal potential reaction effects on the
botanical material, and are neither acidic nor alkaline. At the end of each production cycle, the
processing plant is sealed so that solvents are constantly recycled and totally recovered.
Electricity is the unique utility required to perform these systems and, even then, they consume
little energy. There is no scope for the escape of the solvents, and even if some solvents come to
escape, they pose no threat to the ozone layer because they do not contain chlorine. The waste
product (biomass) from these plants is dry and “ecofriendly” to handle.

Advanced anylatical techniques used in pharmacognocy:

the role of various analytical techniques and their corresponding analytical methods in the
analysis of pharmaceuticals.

Chromatographic techniques
. Thin layer chromatography
Although an old technique yet it finds a lot of application in the field of pharmaceutical analysis.
In thin layer chromatography, a solid phase, the adsorbent, is coated onto a solid support as a thin
layer usually on a glass, plastic, or aluminum support. Several factors determine the efficiency of
this type of chromatographic separation. First the adsorbent should show extreme selectivity
toward the substances being separated so as to the dissimilarities in the rate of elution be large.
For the separation of any given mixture, some adsorbents may be too strongly adsorbing or too
weakly adsorbing
 Thin layer chromatography is a popular technique for the analysis of a wide variety of organic
and inorganic materials, because of its distinctive advantages such as minimal sample clean-up,
wide choice of mobile phases, flexibility in sample distinction, high sample loading capacity and
low cost. TLC is a powerful tool for screening unknown materials in bulk drugs). It provides a
relatively high degree of assertion that all probable components of the drug are separated. The
high specificity of TLC has been exploited to quantitative analytical purpose using spot elution
followed by spectrophotometric measurement. TLC has been utilized for the determination of
some) and noscapine . TLC plays a crucial role in the early stage of drug development when
information about the impurities and degradation products in drug substance and drug product is
inadequate. Various impurities of pharmaceuticals have been identified and determined using
TLC.

High performance thin layer chromatography

With the advancement of the technique, high performance thin layer chromatography (HPTLC)
emerged as an important instrument in drug analysis. HPTLC is a fast separation technique and
flexible enough to analyze a wide variety of samples. This technique is advantageous in many
means as it is simple to handle and requires a short analysis time to analyze the complex or the
crude sample cleanup. HPTLC evaluates the entire chromatogram with a variety of parameters
without time limits. Moreover, there is simultaneous but independent development of multiple
samples and standards on each plate, leading to an increased reliability of results. HPTLC has
been used to quantitate drugs as ethinyl estradiol and cyproterone , alfuzosin and tramadol
and pentazocine.
HPLC is an advanced form of liquid chromatography used in separating the complex mixture of
molecules encountered in chemical and biological systems, in order to recognize better the role
of individual molecules. The specificity of the HPLC method is excellent and simultaneously
sufficient precision is also attainable. However, it has to be stated that the astonishing specificity,
precision and accuracy are attainable only if wide-ranging system suitability tests are carried out
before the HPLC analysis. For the reason the expense to be paid for high specificity, precision
and accuracy is also high.

Gas chromatography:

Moving ahead with another chromatographic technique, gas chromatography is a powerful

separation technique for detection of volatile organic compounds. Combining separation and on-
line detection allows accurate quantitative determination of complex mixtures, including traces
of compounds down to parts per trillions in some specific cases. Gas liquid chromatography
commands a substantial role in the analysis of pharmaceutical product). The creation of high-
molecular mass products such as polypeptides, or thermally unstable antibiotics confines the
scope of this technique. Its main constraint rests in the comparative non-volatility of the drug
substances therefore, derivatization is virtually compulsory. Recently, gas chromatography has
been used for assay of drugs such as isotretinion), cocaine and employed in the determination of
residual solvents in betamethasone valerate. Gas chromatography is also an important tool for
analysis of impurities of pharmaceuticals. In recent years GC has been applied to estimate the
process related impurities of the pharmaceuticals), residual solvents listed as impurity by the
International Conference of Harmonization are analyzed by the GC using a variety of

Spectroscopic techniques

Spectrophotometry

Another important group of methods which find an important place in pharmacopoeias are
spectrophotometric methods based on natural UV absorption and chemical reactions
Spectrophotometry is the quantitative measurement of the reflection or transmission properties of
a material as a function of wavelength.
The advantages of these methods are low time and labor consumption. The precision of these
methods is also excellent. The use of UV–Vis spectrophotometry especially applied in the
analysis of pharmaceutical dosage form has increased rapidly over the last few The colorimetric
methods are usually based on the following aspects:
•Complex-formation reaction.
•Oxidation-reduction process.
•A catalytic effect.
It is important to mention that colorimetric methods are regularly used for the assay of bulk
materials. For example, the blue tetrazolium assay is used for the determination
of corticosteroid drug formulations. The colorimetric method is also exploited for the
determination of cardiac glycosides and is presented in European Pharmacopoeia. Several
approaches using spectrophotometry for determination of active pharmaceutical ingredients in
bulk drug and formulations have been reported.

Near infrared spectroscopy (NIRS)

Near infrared spectroscopy (NIRS) is a rapid and non-destructive procedure that provides multi
component analysis of almost any matrix. In recent years, NIR spectroscopy has gained a wide
appreciation within the pharmaceutical industry for raw material testing, product quality control
and process monitoring. The growing pharmaceutical interest in NIR spectroscopy is probably a
direct consequence of its major advantages over other analytical techniques, namely, an easy
sample preparation without any pretreatments, the probability of separating the sample
measurement position by use of fiber optic probes, and the expectation of chemical and physical
sample parameters from one single spectrum. The major pharmacopoeias have generally adopted
NIR techniques.) address the suitability of NIR instrumentation for application in pharmaceutical
testing. NIR spectroscopy in combination with multivariate data analysis opens many interesting
perceptions in pharmaceutical analysis, both qualitatively and quantitatively

Nuclear magnetic resonance spectroscopy (NMR)

Since the first report appeared in 1996) describing the use of NMR spectroscopy to screen for the
drug molecules, the field of NMR based screening has proceeded promptly. Over the last few
years, a variety of state-of-the-art approaches have been presented and found a widespread
application in both pharmaceutical and academic research. Recently NMR finds its application in
quantitative analysis in order to determine the impurity of the drug, characterization of the
composition of the drug products and in quantitation of drugs in pharmaceutical formulations
and biological fluid.

Fluorimetry and phosphorimetry

The pharmaceutical industries continuously look for the sensitive analytical techniques using the
micro samples. Fluorescence spectrometry is one of the techniques that serve the purpose of high
sensitivity without the loss of specificity or precision.

Electrochemical methods
The application of electrochemical techniques in the analysis of drugs and pharmaceuticals has
increased greatly over the last few years. The renewed interest in electrochemical techniques can
be attributed in part to more sophisticated instrumentation and to increase the understanding of
the technique themselves.

Kinetic method of analysis

Kinetic method of analysis has been developing since 1950s and yet in modern days it is taking a
major resurgence in activity. The repetitive interest in the kinetic methods can be credited to the
advancements made in principles, in automated instrumentation, in understanding the chemical
and instrumentation, in data analysis methods and in the analytical application.

Electrophoretic methods
Another important instrument essential for the analysis of pharmaceuticals is capillary
electrophoresis (CE). CE is a relatively new analytical technique based on the separation of
charged analytes through a small capillary under the impact of an electric field. In this technique
solutes are perceived as peaks as they pass through the detector and the area of individual peak is
proportional to their concentration, which allows quantitative estimations. In addition to
pharmaceutical studies it finds an application in the analysis of biopolymer analysis
and inorganic ions. CE analysis is generally more effective, can be performed on a quicker time
scale, requires only a small amount, lesser up to Nano liter injection volumes, and in most cases,
takes place under aqueous conditions. These four characteristics of CE have proven to be
beneficial to many pharmaceutical applications.

Hyphanated techniques
The coupling of a separation technique and on-line separation technique leads to the
development of a hyphenated technique. The last two decades saw a remarkable advancement in
the hyphenated techniques and its application in pharmaceutical analysis. A variety of
hyphenated techniques such as LC-MS), LC-NMR), CE-ICP-MS) and CE-MS) have been
applied in the analysis of pharmaceuticals. The determination of drugs in biological materials is
an important step in drug discovery and drug development. The determination of drugs in
biological materials is an important step in drug discovery and drug development. HPLC
together with various types of detection such as ultraviolet, fluorescence,and mass spectrometry
has become the method of choice for bioanalytical method development). Recently a review of
HPLC with UV or MS/MS‘ detection is presented for the analysis of meloxicam in biological
samples and pharmaceutical formulations). Liquid chromatography-electrospray ionization–mass
spectrometry method for the qualitative and quantitative determination of metabolites after oral
administration of Rhizome coptidis and Zuojinwan preparation in rat urine has been developed),
the same analytical technique was used for the simultaneous determination of L-ascorbic acid
and acetyl salicylic acid in aspirin C effervescent tablet. Urine samples were separated on a
C18 column using a mixture of water (containing 0.1% formic acid) and acetonitrile (30:70 v/v)
as the mobile phase. Recreational drug abuse is a growing issue and new substances are detected
frequently in clinical and forensic samples. Diphenyl-2-pyrrolidinemethanol is one of these
substances and therefore work has been done to identify it and its metabolites in rat urine using
gas chromatography–mass spectrometry and liquid chromatography–high resolution–mass
spectrometry. Experiments were performed to identify the presence of human pharmaceuticals in
the tropical aquatic environment of Malaysia. Water samples collected at different sites along the
Langat River and effluents from five sewage treatment plants were extracted by solid phase
extraction and analyzed using liquid chromatography coupled with tandem mass spectrometry).
This study confirmed the presence of mefenamic acid, salicylic acid and glibenclamide in all
river water samples. Drug–drug interaction of rabeprazole and clopidogrel in healthy Chinese
volunteers has been studied. The plasma concentrations of rabeprazole and clopidogrel were
analyzed by LC-MS/MS at different time intervals after administration). A novel LC-MS/MS
method has been developed for the detection of carbapenemase activity from bacterial isolates).
A HPLC-MS/MS method has been reported for the determination of six kinds of parabens in
food). The method was successfully applied to the determination of methyl, ethyl, propyl, butyl,
isopropyl and isobutyl esters of 4-hydroxybenzoic acid. To assess the pharmacokinetics of
selective substrates of human cytochrome P450s in mini pigs, caffeine,
warfarin, omeprazole, metoprolol and midazolam were administered in combination either
through intravenous route or orally. Plasma samples obtained upto 24 h after dosing were
analyzed by liquid chromatography–tandem mass spectrometry to estimate typical
pharmacokinetic parameters for each analyte.