Pharmaceutical Analytical Chemistry
(Introduction)
1st Lecture
By:
Dr. Hemn A. Qader
What is the Chemistry?
Chemistry is the science of the composition, structure, properties and
reactions of matter, especially of atomic and molecular systems. Life itself is full
of chemistry; i.e., Body life is the reflection of a series of continuous
biochemical processes. Right from the composition of the cell to the whole
organism, the presence of chemistry is conspicuous. Human beings are
constructed physically of chemicals.
In our everyday life, whatever we see, use or consume is the gift of
research in chemistry for thousands of years. In fact, chemistry is applied
everywhere in modern life. It has played a major role in pharmaceutical
advances, forensic science and modern agriculture. Diseases and their remedies
have also been a part of human lives. Chemistry plays an important role in
understanding diseases and their remedies, i.e. drugs.
Medicines or drugs that we take for the treatment of various ailments are
chemicals, either organic or inorganic. However, most drugs are organic
molecules. Let us take aspirin as an example. It is probably the most popular and
widely used analgesic drug because of its structural simplicity and low cost.
Aspirin is chemically known as acetyl salicylic acid, an organic molecule. The
precursor of aspirin is salicin, which is found in willow tree bark. However,
aspirin can easily be synthesized from phenol using the Kolbe reaction.
In order to have a proper understanding and knowledge of these drugs and
their behavior, there is no other alternative but to learn chemistry. Everywhere,
from discovery to development, from production and storage to administration,
1
and from desired actions to adverse effects of drugs, chemistry is involved
directly. (How?) see the
“CHEMISTRY FOR PHARMACY STUDENTS (General Organic and Natural
Product Chemistry)” by Sarker & Nahar
Analytical chemistry is the branch of chemistry science which deals with the
study of the separation, identification, and quantification of
the chemical components of natural and artificial materials.
Analytical chemistry is a measurement science consisting of a set of powerful
ideas and methods that are useful in all fields of science and medicine.
Figure (1): The relationship between analytical chemistry, other branches of
chemistry, and the other sciences
The central location of analytical chemistry in the diagram signifies its
importance and the breadth of its interactions with many other disciplines.
Analytical chemists assess the chemical structure and nature of
substances. Their skills are needed for a variety of purposes including drug
2
development, forensic analysis and toxicology. Analytical chemists can
specialize in areas as varied as toxicology, pharmaceuticals and forensics, due to
that most analytical chemists work for private research and development firms,
while another large portion work for pharmaceutical companies or testing labs.
Pharmaceutical Analytical Chemistry:
The branch of chemistry that deals with the separation , identification and
determination of drugs.
Pharmaceutical Analytical Chemistry or (pharmaceutical analysis as a
short name) is the scientific discipline of analytical chemistry applied to
pharmaceuticals. Examines various analytical techniques commonly used in
pharmaceutical laboratories.
Pharmaceutical Analytical Chemistry enables pharmacy students to gain
fundamental knowledge of the vital concepts, techniques and applications of the
chemical analysis of pharmaceutical ingredients, final pharmaceutical products
and drug substances in biological fluids. A unique emphasis on pharmaceutical
laboratory practices, such as sample preparation and separation techniques,
provides an efficient and practical educational framework for undergraduate
studies in areas such as pharmaceutical sciences, analytical chemistry and
forensic analysis. It introduces the common analytical methods used in
quantitative and qualitative chemical analysis of pharmaceuticals.
In the context of pharmaceutical sciences, analytical chemistry is the
branch of science that provides knowledge of compound separation,
identification and quantification that can be useful for measuring bioavailability
of drugs, purifying drugs during synthesis, and identifying drug metabolic
pathways. To accurately quantify drugs and metabolites in pharmacokinetic,
transport, and delivery studies, a strong understanding of analytical chemistry
principles is necessary and only well-characterized analytical methods should be
used to ensure the integrity of collected data, as shown in the Figure (2).
3
Figure (2): Application of analytical techniques (PK: pharmacokinetics; PD:
pharmacodynamics; TDM: Therapeutic Drug Monitoring)
Analytical science and pharmaceutical quality (ASPQ) are one of the most
important and challenging disciplines in pharmaceutical drug discovery,
development and manufacture. Quality control based on analytical science is
necessary and indispensable for safety and effective use of medicine.
Development of New Pharmaceutical and Use
New active pharmaceutical ingredients (APIs) are developed by
pharmaceutical companies, based on drug discovery research and subsequent
preclinical development. Drug discovery recalls innovation and heavy research
activities. In this work, new chemical/biochemical substances are identified and
tested for their pharmacological activity. A successful drug candidate is then
tested in animals for its effect and for its toxicity. At this stage the absorption,
distribution, metabolism, and excretion (abbreviated to ADME) of the drug
candidate are studied and the appropriate dose is settled. Pharmaceutical
analysis is involved in all parts of these processes for characterization,
4
identification, and quantitation of the drug candidate as a pure substance, in
preparations and in blood, urine, and tissue samples.
At the start of any medication, it is common to treat patients with a
standard dose, but it is well known that different patients may exhibit large
variations in response to a given pharmaceutical product. In such cases it is
important to adjust the dose. One example is the treatment of hypertension. The
dose may be reduced when blood pressure is too low, and the dose may be
increased when blood pressure is too high. For other types of treatment, such as
depression, psychosis, and epilepsy, the efficacy of the medication is more
challenging to evaluate, and in those cases therapeutic drug monitoring (TDM)
is advised. In TDM a blood sample is collected from the patient and analysed to
ensure that the drug level is appropriate. The analysis of drugs in biological
fluids is termed bioanalysis. In addition to TDM, and the previously mentioned
ADME studies, bioanalysis is crucial in drug development programs (clinical
trials) and for the detection of drugs of abuse in biological samples (blood,
urine, saliva) from humans (forensic investigations and doping control).
Analytical techniques in pharmaceutical industry
Within the pharmaceutical industry, there are three broad analytical
techniques adopted for determining structure, separating analytes, and
quantifying target molecules. These include classical analytical chemistry
methods, chromatography, and spectroscopy. A common classical analytical
approach is using the titrimetric method, which is a quick qualitative technique
for determining the presence of a particular analyte or pharmaceutical
ingredient.
The optimization of function group procedures has allowed for the
analysis of kinetic measurements to establish reaction rates. Within the
pharmaceutical industry determination of certain pharmaceutical ingredients
such as captopril, gabapentin, and sparfloxacin in commercial dosage forms
using these methods have been achieved.
5
Chromatography methods have a strong presence in the pharmaceutical
industry due to their accuracy of separation and detection. Thin-layer
chromatography (TLC) is a technique for screening unknown materials in bulk
drugs. It provides a qualitative approach in that all likely constituents of the drug
are separated. An advanced version of the technique is high-performance TLC,
which has the advantage of a faster run time to analyze complex mixtures and
multiple samples or drugs.
Furthermore, high-performance liquid chromatography (HPLC) is used to
separate complex mixtures and has high specificity, precision, and accuracy.
There are several detectors used for HPLC, but a commonly used detector is UV
due to its capability of monitoring various wavelengths at once. HPLC can
analyze several drugs in the pharmaceutical formulation process and has been a
dominating technique in the industry. Moreover, when coupled with mass
spectrometry (LC-MS) it has been a new gold standard for quality control and
assurance within the industry. Another chromatography separation technique
typically used in industry is gas chromatography, which detects volatile organic
compounds. It is used in the pharmaceutical industry to analyze impurities and
residual solvents.
Alternatively, spectroscopic methods play an important role in the
pharmaceutical industry because they are low-cost, fast, and highly accurate.
Common analytical techniques used are Raman and infrared spectroscopy. Near-
infrared spectroscopy (NIRS) is most widely used in the pharmaceutical industry
and is a rapid and non-destructive procedure that can analyze almost any matrix.
It is mainly used for raw material testing, quality control, and process
monitoring. It has general acceptance in the pharmaceutical industry because of
easy sample preparation to detect physicochemical properties from a single
spectrum.
Hence, the role of analytical chemistry in the pharmaceutical industry
mainly lies in the efficient and effective detection and characterization of
6
pharmaceutical ingredients for maintaining high-quality assurance and quality
control.
From the discussions above, it appears that pharmaceutical analysis plays
a major role in the life cycle of pharmaceuticals. Thus, pharmaceutical analysis
is important for people working in the pharmaceutical industry, hospital
laboratories, contract analytical laboratories, pharmaceutical and medical
research institutions, and institutions investigating cases of drug abuse and
doping in sports (forensic and doping laboratories)
https://www.wiley.com/en-
iq/Introduction+to+Pharmaceutical+Analytical+Chemistry+2e-p-
9781119362722
Some terms in analytical chemistry and pharmaceutical
analytical chemistry
• (Identification) Qualitative analysis reveals the identity of the elements
and compounds in a sample. This analysis can be done in different way,
such as; colour, smell, boiling point, solubility, and some other physical
parameters like refractive index, optical activity ...etc.
Detection: does the sample contain substance X?
Identification: what is the identity of the substance in the sample?
• (Determination) Quantitative analysis indicates the amount of each
substance in a sample.
How much of substance X is in the sample?
A quantitative investigation means that the amount (quantity) or relative
amount of each component present is determined. In a pure substance, the
entire mass, or 100%, is composed of a single component. In materials
composed of two or more substances, a quantitative investigation would
determine the mass or relative mass present for each component within the
sample. It is not always necessary to find quantitative values for all components
that make up a substance. In most cases it is sufficient to analyze the material for
7
one or perhaps more components of interest. The amount of API within an
antacid tablet, for example, is significant, whereas the fillers, binders, colorants,
and flavoring agents present are of lesser importance.
• Analytes are the components of a sample that are to be determined.
Sample is analyzed while analyte is determined, like Blood sample is analyzed
while cholesterol is determined.
What is assay in pharmaceutical analysis?
An assay is an investigative (research) procedure in medical laboratory,
pharmacology, environmental biology and molecular biology for qualitatively
assessing or quantitatively measuring the presence, amount, or functional
activity of a target entity (the analyte).
Analytical methods can be classified to classical and instrumental methods.
Analytical
Methods
Modern
Classical Methods
Methods
(Instrumental)
Volumetric Gravimetric
Analysis Analysis
Classical methods (also known as wet chemistry methods) use extraction,
precipitation, and distillation procedure as a separation techniques and
qualitative analysis can be performed by color, odor, or melting point. Classical
quantitative analysis is achieved by measurement of weight or volume.
8
Volumetric Analysis (Analysis by volume)
In this method measuring the volume of a solution containing sufficient
reagent to react completely with the analyte in the titration procedure.
Gravimetric Analysis (Analysis by mass)
In this method measuring the mass of the analyte or some compound
chemically related to it.
Instrumental methods use an apparatus to measure physical quantities of the
analyte such as light absorption, fluorescence, or conductivity. The separation of
materials is accomplished using chromatography, electrophoresis or Field Flow
Fractionation methods.
