SAS 1 LECTURE NOTES of entering chemical change and is a
combination of atoms of the same kind or
ANALYTICAL CHEMISTRY- is a
measurement science consisting of a set of
powerful ideas and methods that are useful
in all fields of science, engineering, and
medicine.
CHEMISTRY - it is defined as the science
that deals with the study of the changes in
composition which matter undergoes and
the transformation of energy accompanying
these changes.
MATTER - is anything that has weight and
occupies space (Solid, Liquid and Gas)
PROPERTIES OF MATTER
PHYSICAL - it is how the matter appears in
nature
a. INTRINSIC - (AKA intensive)
properties are properties that are
within the substance. These
properties do not depend on the
amount of material that you have.
Examples: Melting point, boiling
point, density, odor, and color
b. EXTRINSIC - (AKA extensive)
properties are properties that depend
on the amount of the substance you
have. All size measurements depend
on amount, so all size measurements
are extrinsic properties.
Examples: Mass, volume, and heat
content
CHEMICAL - the property that enters
chemical reactions
PHYSIOLOGICAL - the physiological
behavior when taken into the body
CHANGES OF MATTER
PHYSICAL - involves in the changes in
form and appearance, but without affecting
their chemical nature.
CHEMICAL - involves the change in its
composition
CLASSIFICATION OF MATTER
ATOM - the smallest particle of an element
which enters a chemical combination,
composed of a nucleus and around it
revolves the electrons.
MOLECULE - is the smallest particle of
matter that can exist in a free state capable
different atoms.
ELEMENT - simplest particle of matter
which is incapable of being divided and can
enter chemical combination. It cannot be
decomposed into simpler materials by
ordinary processes.
MIXTURE - is a mass if ingredients with a
variable proportion.
a. HETEROGENOUS MIXTURE - is a
combination of 2 or more substances
which can be separated one from the
other by mechanical means
(Filtration, floatation, centrifugation,
distillation, fractional distillation,
fractional distillation, fractional
crystallization, chromatography).
b. HOMOGENOUS MIXTURE - is a
combination of 2 or more substances
which cannot be separated from one
another by mechanical means, even
by filtration and decantation.
COMPOUND - is a combination of two or
more elements at a definite proportion. It
must conform to a general law that a
compound would always have definite
composition at a definite proportion.
COMPOUND CHARACTERISTICS
• They cannot be separated into their
component substance by chemical
means.
• They are homogenous in composition.
• They have definite proportion by
weight of the substance from which
they were made
CLASSIFICATION OF COMPOUND
ACCORDING TO THE NUMBER OF
ELEMENTS PRESENT
• Binary (2)
• Ternary (3)
• Quaternary (4)
ACCORDING TO FORM
1. ISOMORPHOUS - termed applicable
if the different compounds crystallize
in the same form which is also known
as isomorphism.
Examples: Potassium permanganate
& potassium chlorate
2. POLYMORPHOUS - compounds with the prefix hydro. The stem of
forming 2 or more different types of the anion has the suffix –ic and it
crystals also known as is followed by the word acid. (ex.
polymorphism. H2S=hydrosulfuric acid and HF =
Examples: Carbon hydrofluoric acid) or all binary
3. METAMORPHOUS - the same acids have a prefix of –hydro and
compound but they can be changed a suffix of –ic.
into one form to another. 2. When the anion ends in –ite, like
Examples: Chalk—which can be sulfite, the acid name is the name
changed to marble, having the same of the anion with the suffix –ous
chemical formula as calcium fillowed by the word acid. (ex.
carbonate (CaCO3) H3PO3 where X=phosphite =
4. ISOMERIC - a class of organic Phousphorous acid).
compounds in which compounds 3. If the anion name ends in –ate
having the same molecular formula such as nitrate, the acid name is
but differs in physical and chemical the anion with the suffix –ic,
properties and the phenomenon is followed by the word acid. HNO3
termed as isomerism. X=nitrate = Nitric acid).
Examples: ethyl alcohol and
BASE – a substance that produces
dimethyl ether
hydroxide ion when dissolved in water.
5. POLYMER - is a class of organic
Ionic compounds that are bases are named
compounds in which two or more
as any other compounds: the name of the
compounds have the same
cation is written first allowed by the name
percentage of elements present in the
of the anion.
compound. If the molecules of the
compound is taken twice, it is termed PROPERTIES OF BASE
as Monomer, if more than twice it is
termed as polymer and the • Bitter in taste
phenomenon is termed • Neutralizes acids
polymorphism. • Proton acceptor
• pH above 7
ACCORDING TO ITS BEHAVIOR AS • It feels smooth
ACIDS, BASE AND SALTS • Soothing and slippery skin is
ACIDS - is a substance that produces breaking
hydrogen ion when dissolved in water. • Turn red litmus paper to blue
(formula=HX; where X is a monoatomic
SALTS - defined as a substance whose
or polyatomic anion.
water solution contains a positive ion other
BRONSTED – LOWRY THEORY - an than the hydrogen ion and a negative ion
acid is a proton donor other than the hydroxide ion.

LEWIS ELECTRONIC THEORY - an ATOM

acid is an electron acceptor • It is defined as the smallest particle

of an element that retains its
PROPERTIES OF ACIDS chemical identity
• Sour in taste • It was Democritus (460-370 BC, a
• Neutralizes base Greek philosopher who proposed
• Donor of proton that all matter is composed of tiny
• pH below 7 indivisible particles and called these
• Feels like water on normal skin particles atomos which meant
but it stings indivisible or indestructible.
• turn red litmus paper to red • Atom has three subatomic particles,
the electron, proton and neutron.
RULES IN NAMING ACIDS • An atom has a small, dense nucleus
1. When the name of the anion (X) that contains protons and neutrons.
ends in –ide, the acid name begins • Most of the mass of the atom is
concentrated in the nucleus.
• Collectively, the protons and
neutrons are called nucleons. The
electron is found in the region
surrounding the nucleus.
• Protons (+) and electrons (-) are
electrically charged particles, and the
neutron has no charge.
• Mass number (A) is the number of
protons + number of neutrons
while Atomic number (Z) is the
number of protons equal to the
number of electrons.
JOHN DALTON’S ATOMIC THEORY
• Also known as the Law of
Conservation of Mass
• Atom cannot be created or destroyed
• Each element is composed of
extremely small particles called
atoms
• All atoms of a given element are
identical to one another in mass
other properties, but the atoms of
one element are different from the
atoms of the other elements
• The atoms of one element cannot be
changed into atoms of a different
element by chemical reactions;
atoms are neither created nor
destroyed in the chemical reactions
• Compounds are formed when atoms
of more than one element combine a
given compound always has same
relative number and kind of atoms.
OTHER ATOMIC THEORIES
JOSEPH JOHN THOMSON
• Proposed that atom is sphere of
positive (+) particles to which are
embedded with negative particles.
• He developed the Raisin-Bread Model
or Plum-Pudding Model.
ERNEST RUTHERFORD
• He disproved Thomson’s model by
using “Gold Foil/Film Experiment” in
which he concluded that atom is just
an empty space
• The nucleus accounts for the positive
charge & mass of the atom then
electrons are scattered around the
nucleus.
• He developed the Nuclear Model
NEILS BOHR
• Developed the ‘Planetary Model’ of
atom in which he proposed that atom
consists of nucleus and surrounded
by electrons which are travelling in
circular orbits called orbitals.
ERWIN SCHRODINGER
• Developed the “Quantum Mechanical
Model” and this is considered the
modern atomic structure.
DIVISION OF CHEMISTRY
PURE
• Inorganic
• Organic
• Physical
• Analytical
APPLIED
• Industrial
• Pharmaceutical Chemistry
THE ROLE OF ANALYTICAL
CHEMISTRY
• Analytical chemistry is applied
throughout industry, medicine, and
all the sciences.
• Quantities of hydrocarbons, nitrogen
oxides, and carbon monoxide present
in automobile exhaust gases are
measured to determine the
effectiveness of emission-control
devices.
• Quantitative measurements of
ionized calcium in blood serum help
diagnose parathyroid disease in
humans. Quantitative determination
of nitrogen in foods establishes their
protein content and thus their
nutritional value.
• Quantitative analytical
measurements also play a vital role
in many research areas in chemistry,
biochemistry, biology, geology,
physics, and the other sciences.
• Analytical chemistry has a similar
function with respect to the many
other scientific fields listed in the
diagram. Chemistry is often called
the central science; its top center
position and the central position of
analytical chemistry in the figure
emphasize this importance.
• The interdisciplinary nature of
chemical analysis makes it a vital
tool in medical, industrial,
government, and academic
laboratories throughout the world.
 QUANTITATIVE ANALYTICAL
METHODS
• We compute the results of a typical
quantitative analysis from two
measurements. One is the mass or
the volume of sample being analyzed.
• The second measurement is of some
quantity that is proportional to the
amount of analyte in the sample
such as mass, volume, intensity of
light, or electrical charge. This
second measurement usually
completes the analysis, and we
usually classify analytical methods
according to the nature of this final
measurement.
• In gravimetric methods, we
determine the mass of the analyte
or some compound chemically
related to it.
• In a volumetric method, we measure
the volume of a solution containing
sufficient reagent to react completely
with the analyte.
• In electroanalytical methods, we
measure electrical properties such as
potential, current, resistance, and
quantity of electrical charge.
• In spectroscopic methods, we
explore the interaction between
electromagnetic radiation and
analyte atoms or molecules or the
emission of radiation by analytes.
• In a group of miscellaneous methods,
we measure such quantities as
mass-to-charge ratio of ions by mass
spectrometry, rate of radioactive
decay, heat of reaction, rate of
reaction, sample thermal
conductivity, optical activity, and
refractive index.
A TYPICAL QUANTITATIVE
ANALYSIS
1) CHOOSING A METHOD
• The essential first step in any
quantitative analysis is the selection
of a method
• One of the first questions that must
be considered in the selection
process is the level of accuracy
required.
• The selected method usually
represents a compromise between
the accuracy required and the time
and money available for the analysis.
• A second consideration related to
economic factors is the number of
samples that will be analyzed.
2) ACQUIRING THE SAMPLE
• The second step in a quantitative
analysis is to acquire the sample. To
produce meaningful information, an
analysis must be performed on a
sample that has the same
composition as the bulk of
material from which it was taken.
3) PROCESSING THE SAMPLE
• The third step in an analysis is to
process the sample. Under certain
circumstances, no sample
processing is required prior to the
measurement step.
➢ Preparing a Laboratory Sample
➢ Defining Replicate Samples
➢ Preparing Solutions: Physical
and Chemical Changes
4) ELIMINATING
INTERFERENCES
• Once we have the sample in solution
and converted the analyte to an
appropriate form for measurement,
the next step is to eliminate
substances from the sample that
may interfere with measurement.
5) CALIBRATING AND
MEASURING CONCENTRATION
• All analytical results depend on a
final measurement X of a physical or
chemical property of the analyte, as
shown in Figure 1-2. This property
must vary in a known and
reproducible way with the
concentration cA of the analyte.
6) CALCULATING RESULTS
• Computing analyte concentrations
from experimental data is usually
relatively easy, particularly with
computers. These computations are
based on the raw experimental data
collected in the measurement step,
the characteristics of the
measurement instruments, and
the stoichiometry of the analytical
reaction.
7) EVALUATING RESULTS BY
ESTIMATING RELIABILITY
• Analytical results are complete only
• when their reliability has been
estimated. The experimenter must
provide some measure of the
uncertainties associated with
 computed results if the data are to
have any value.
FEEDBCAK LOOP – the cycle of
measurement, comparison, and control
FEEDBACK SYSTEM – the process of
continuous measurement and control
QUALITATIVE ANALYSIS - reveals the
identity of the elements and compounds
in a sample
QUANTITATIVE ANALYSIS - indicates
the amount of each substance in a
sample
ANALYTES - are the components of a
sample that are determined
ASSAY - is the process of determining how
much of a given sample is the material by
its indicated name
REPLICATE SAMPLES/REPLICATES- are
portions of a material of approximately the
same size that are carried through an
analytical procedure at the same time and
in the same way
INTERFERENCE/INTERFERENT- s a
species that causes an error in an analysis
by enhancing or attenuating (making
smaller) the quantity being measured
SAMPLE MATRIX/MATRIX- is the
collection of all the components in the
sample containing an analyte
CALIBRATION - is the process of
determining the proportionality between
analyte concentration and a measured
quantity
SAS 2 LECTURE NOTES
ELECTROLYTES & BLOOD CHEMISTS -
are usually the first set of laboratory tests
ordered upon initial patient presentation
BASIC METABOLIC PANEL (BMP)
• Sodium (Na)
• Potassium (K)
• Chloride (Cl)
• Carbon dioxide (CO2)
• Glucose
• Blood urea nitrogen (BUN)
• Creatinine
COMPREHENSIVE METABOLIC PANEL
(CMP)
• Albumin
• Alkaline phosphatase
• Alanine Aminotransferase (ALT),
• Aspartate aminotransferase (AST)
• total bilirubin
• Calcium
OTHER BIOCHEMICAL PROFILE
• SMA – 6
• SMA – 12
• Chem Profile 20
GRAVIMETRIC METHOD – determine the
mass of the analyte or some compound
chemically relate to it.
➢ Precipitation– substance to be
determined is converted to an
insoluble precipitate which is
collected and weighed
➢ Volatilization – analyte r its
decomposing products are volatized
a, collected and weighed
VOLUMETRIC/ TRITIMETRIC
METHOD – measure the volume of the
solution containing sufficient reagent to
react completely with the analyte (e.g.
Acid-Base and Redox).
ELECTROANALYTICAL METHOD –
involve the measurement of such
electrical properties as potential,
current, resistance and quantity of
electrical charge
➢ Voltammetry – measurement of
current as a function of the
applied voltage and reveals the
reduction potential of an analyte
➢ Coulometry -- measurement of the same basic principles as
current and time needed to Radioimmunoassay (RIA) except that
complete an electrochemical enzyme activity rather than
reaction and reveals radioactivity is measured. This assay
concentration of an analyte. is commonly used in serologic tests
➢ Potentiometry – measurement to determine antibodies directed
of potential of an ion electrode in against a wide range of antigens such
equilibrium with an ion to be as rheumatoid factor, hepatitis B
determined and reveals antigen, other bacterial and viral
concentration of an analyte. antigen (e.g. cytomegalovirus, HIV…)
in the serum
SPECTROSCOPIC METHODS – it is ENZYME MULTIPLIED
based on the measurement of the IMMUNOASSAY (EMIT) – it is a
interaction between electromagnetic homogeneous EIA in which the
radiation and analyte atoms or enzyme is used as a label for a
molecules or on the production of specific analyte especially in testing
such radiation by analytes. general chemistries (e.g. albumin,
BUN, creatinine, glucose,
ION-SELECTIVE ELCTRODES (ISE)
cholesterol, bilirubin, total protein),
– ionization of molecules introduced
enzymes (e.g. acid and alkaline
into a Mass Spectrometry (MS)
phosphatase, amylase, creatinine
involves ionization of molecule in the
kinase), coagulation factors (e.g.
gas phase according to their mass to
antithrombin III, fibrinogen,
charge ration (m/z). This assay is
degradation products, heparin,
commonly used to test for
plasminogen) and some drugs for
electrolytes.
therapeutic drug monitoring (e.g.
GAS CHROMATOGRAPHY (GC) – it aminoglycosides, vancomycin,
is use to identify and quantify volatile digoxin, antiepileptics,
substances such as alcohols. For antiarrhythmics, theophylline) and
toxicological screening of organic for drug level toxicology (e.g.
acids, and drugs (e.g. steroids, acetaminophen, salicylate,
benzodiazepines and tricyclic barbiturates, TCAs, amphetamines,
antidepressant). Has similar cocaine, opiates).
principle with thin layer
FLUORESCENT POLARIZATION
chromatography but instead of
IMMUNOASSAY (FPIA) -- the most
solvent, GC utilizes an inert gas (e.g.
common form of immunoassay, is
helium, nitrogen) as a carrier for the
used to measure concentrations of
volatile substance.
many serum analytes such as BUN
HIGH PERFORMANCE LIQUID and creatinine. This assay is
CHROMATOGRAPHY (HPLC) – it is commonly used for therapeutical
widely used, especially in forensic drug monitoring of some drugs (e.g
laboratories, for toxicological aminoglycosides, vancomycin,
screening, amino acids and drugs antiepileptics, antiarrhythmics,
(e.g. indomethacin, anabolic theophylline, methotrexate, digoxin,
steroids, cyclosporine). It has similar cyclosporine), general chemistries
principle with GC but it is useful in and enzyme (e.g., thyroxine,
non-volatile or heat sensitive triiodothyronine, cortisol, amylase,
substance but instead of gas, HPLC BUN, lactate dehydrogenase,
utilizes a liquid solvent (mobile creatinine, glucose, cholesterol and
phase) and a column packed with a iron).
stationary phase (e.g. silica base).
POLYMERASE CHAIN REACTION
ENZYME-LINKED (PCR) – is the most frequently is the
IMMUNOSORBENT ASSAY (ELISA) most frequently used in Nucleic Acid
– it is a heterogeneous Enzyme Amplification. This is also used
Immunoassay (EIA) which employs principally for detecting
 microbiological organisms and
genetic disease including chlamydia,
cytomegalovirus, Epstein-Barr virus,
human immunodeficiency virus,
mycobacterium, and herpes simplex
virus.
ELECTROLYTES
• Electrolytes are classified as either
anions (negatively charged) that
moved toward an anode, or cations
(positively charged) ions that moved
toward the cathode.
• Physiological electrolytes include
Na+, K+, Ca2+, Mg2+, Cl-, HCO3-,
HPO4-, H2PO42-, SO42-, and some
organic anions (e.g., Lactate).
• The intracellular fluids contain K+,
Mg2+, and PO4 -,2- ions, whereas
extracellular fluids (interstitial and
plasma-vascular fluids) holds the
sodium, chloride, and bicarbonate
ions. In case an imbalance
concentration occurs, products like
electrolytes, acids, base, blood
products, carbohydrates, proteins,
and amino acids can be found.
• Electrolyte determination can be
obtained from blood collected by
venipuncture into an evacuated
tube. Serum electrolyte
concentrations are among the most
commonly used laboratory tests by
clinicians for assessment of a
patient’s clinical condition and
disease state.
SODIUM
NORMAL VALUES: 135-147 mEq/L
PROPERTIES
• This ion belongs in Group IA (Alkali
metal / Soluble group) in the periodic
table together with Li, K, Rb, Cs, Fr
• Found abundantly and widely
distributed in nature, but always in
combination
• A component of many minerals, and
an essential element for animal life
• “Dietary inorganic macro-mineral”
• Predominant cation in the
extracellular fluid
• Common cation of choice to optimize
the pharmaceutical utility of organic
medicaments
• The normal daily diet contains 8-15 g
(130-260mmol) of NaCl, and the body
only requires 1-2 mmol/day, and the
excess is excreted by the kidneys,
which are the ultimate regulators of
the amount of sodium in the body.
PRECAUTIONS
• Sodium promotes water retention in
the tissues thus should be given in
caution in patient with cardiac and
renal condition in which edema is a
problem
• Excess levels of sodium/salt may
indicates:
➢ High blood pressure
➢ Stroke
➢ Heart failure
➢ Osteoporosis
➢ Stomach Cancer
➢ Kidney Disease and kidney
stones
• Sodium citrate (Na3C6H7O5) can
incorporated in blood sample
collection tube to avoid blood
corpuscle adhering to inner wall and
maximum reduction of blood sample
haemocytolysis.
• Sodium Chloride (NaCl) in the most
common salt that is use as an
electrolyte replenisher
OTHER INFORMATION
• Specimens assayed for sodium include
serum, heparinized plasma, whole
blood, sweat, urine, feces or
gastrointestinal fluids.
POTASSIUM
NORMAL VALUES: 3.5-5.2 mEq/L
• It is derived from Kalium “the calcined
ashes”; which originally meant potash,
an alkali extracted in a pot from the ash
of burnt wood or tree leaves
• Easily oxidized (kept in kerosene,
benzene, or liquid petrolatum)
• Makes glass amber-colored or light
resistant
PHARMACOLOGICAL ACTIONS
• Predominant intracellular cation
necessary for cell growth and
function
• possesses an osmotic diuretic effect
 ➢ Order of diuretic efficiency:
nitrate > chloride > ACh)
bicarbonate = acetate = citrate
• Potassium supplements should not
be administered by rapid IV injection
• Deficiency of K
(hypokalemia/hypopotassemia) may
occur by:
➢ diarrhea
➢ hemorrhage
➢ diabetic coma
➢ vomiting
SYMPTOM/S: muscle weakness
REMEDY: KCl (IV), Darrow’s solution (KCl
+ NaCl with Na lactate)
• Excess K
(hyperkalemia/hyperpotassemia):
diastolic arrest
REMEDY: IV injection of NaCl, CaCl2,
calcium gluconate, or dextrose
OTHER INFORMATION
• Specimens assayed for sodium
analysis are generally applicable to
those for K+ analysis.
MAGNESIUM
NORMAL VALUES: 1.5-2.6 mg/L
• A group IIA (Alkali Earth metals:
Be,Mg, Ca, Sr, Ba, Ra) ion which
came from the origin, magnesia
• Widely and abundantly distributed in
nature
• Second most abundant cation
intracellularly
• Element present in chlorophyll
• Occurs in bones (as Mg3(PO4)2)
• A component of “Flash-light”
powders (a mixture of powdered Mg
and K chlorate or barium peroxide)
➢ Used in pyrotechnics, tracer
bullets, fire-bombs, and night
flares
PHARMACOLOGICAL ACTIONS
• CNS depressant in obstetrics,
convulsant states, and symptoms of
tetanus
➢ Exerts blocking action to
acetylcholine at the
neuromuscular junction
(similar to curare: depresses
sensitivity of the muscle to
• Antidote: Calcium
• Natural calcium blocker
• Saline laxative
• Magnesium sulfate heptahydrate is
one of the most important compound
of Magnesium that is use as Saline
cathartic, Antidote for barium and
barbiturate poisoning
Anticonvulsant in eclampsia (IM),
Depressant in seasickness, HTN,
tetanus spasm, and convulsions (as IV
or IM), Used in paroxysmal auricular
and ventricular tachycardia (IV)
CALCIUM
NORMAL VALUES: 8.5-10.8mg/dL
• Never found free in nature
• Present inside the cell but most
abundant outside the cell
• Present in bones and teeth as apatite
(Ca3(PO4)2)
• In nonluminous flame, imparts a brick
red color (reddish-yellow color)
PHARMACOLOGICAL ACTIONS
• Essential in the maintenance of normal
body functions:
➢ Important cation for the normal
functioning of the ANS
➢ Important factor in cardiac
function
➢ Factor in blood coagulation
➢ Structural basis of the skeleton
• Absorbed in the upper portion of the
intestinal tract
• Possesses a cardiac action similar to
digitalis
➢ High Ca concentrations increase
toxicity of digitalis
• Excess Ca: systolic arrest (while excess
K: diastolic arrest)
• Absorption is enhanced with Vitamin D
• Controls and relieves various allergic
manifestations (e.g. eczema, pruritus,
urticaria)
• Insoluble Ca salts are used as antacids
(e.g. CaCO3, tribasic Ca3(PO4)2)
• Calcium chloride (Muriate of Lime) is a
components of Ringer’s & Lactated
Injection which are used as electrolyte
• It is can also decrease blood clotting
time.
• Calcium citrate • Element present in all acids
• Burns in air with a pale-blue,
nonluminous flame
CHLORINE
PHOSPHOROUS
NORMAL VALUES: 95-106mEq/L
• Occurs in combination as calcium
• From chloros meaning “greenish-
phosphate (aka phosphorite or
yellow”
phosphate rock)
• Aka dephlogisticated marine acid or
• Occurs in bones and teeth (58%
dephlogisticated muriatic acid
calcium phosphate), blood, urine, and
• It is a Halogen ( F, Cl, Br, I, At) which
in nervous, muscle, and brain tissue
also referred as salt forming group.
(as phosphoproteins)
• It is the most abundant anion
• Lethal poison (large doses)
outside the cell.
• Antidote for P poisoning: CuSO4 or
• Hydrochloric acid (Gastric acid,
blue vitriol
Muriatic acid) is the only acid found
in the GIT. Achlorhydria is a OXYGEN
condition associated to the
• Also called:
absence of HCl in the GIT.
➢ Empyreal air (Scheele) – only
known supporter of
PHOSPHATES: Hydrogen Phosphate
combustion
(-HPO4-2), diHydrogen Phosphate
➢ Fire air (Scheele)
(-H2PO4-)
➢ Dephlogisticated air
(Priestley) - oxygen does not
PHOSHATE is important and widely
burn, it only supports
distributed in human body. In blood,
combustion
organic phosphate esters are located
➢ Acid former (Lavoisier) – once
primarily within cells and
thought as a constituent of all
incorporated into nucleic acids,
acids
phospholipids, phosphoproteins and
• Most abundant essential element in
high-energy compounds such as
adenisone thriphosphate (ATP) . the universe
Inorganic phosphate is a major USES:
components of hydroxyapatite in
bone. • Pharmaceutical inhalant – used in
pathological conditions (e.g.
OTHER INFORMATION pneumonia, angina, asthma,
• Inorganic phosphate is the fraction bronchitis, conditions accompanied
measured in serum and plasma in by cyanosis and dyspnea)
clinical laboratories. • Component of “artificial air” (20%
Oxygen and 80% Helium) – used to
HYDROGEN alleviate difficult respiration
• Recognized by Paracelsus • For oxidation
• Produced by Cavendish by the action reactions/combustion – required for
of dilute HCl and H2SO4 and called burning
it inflammable air TRACE ELEMENTS - are inorganic
• Named by Lavoisier as hydrogen micronutrients present at very low
which means water-former concentrations in body fluids and tissue.
SELENIUM
PROPERTIES • From the Greek selene meaning
“moon”
• Lightest gas and the lightest of all
• It belongs in group VIA together
elements
with oxygen, sulfur, tellurium and
• Powerful reducing agent
polonium
• Combustible but does not support
combustion
• Rarely occurs in its elemental state
in nature
• Uses:
➢ Used in glass industry to
make red-colored glass
➢ Essential trace element
➢ Antioxidant, synergistic with
Vitamin E
• ---Deficiency of Se will result to
Keshan disease; If the deficiency is
also associated with iodine, it will
result to Kashin-Beck disease.
IODINE
• From iodes meaning “violet”
• Bluish-black rhombic plates that
stains the skin brown
• Normal constituent of the thyroid
gland
• Uses:
➢ Essential for thyroid function
➢ Antiseptic
➢ Expectorant (iodide ion)
➢ Iopanoic acid, USP
visualization of gall bladder
• Preparation:
➢ henolated iodine solution
(Boulton’s solution)
antibacterial and irritant
➢ Polyvinylpyrrolidone + Iodine
(Povidone-Iodine, Betadine®)
– antiseptic
• Iodides (e.g. NaI, KI) – enhance the
solubility of iodine
• Antidote for iodine toxicity:
cornstarch and sodium thiosulfate
FLUORIDE
• From Greek fluo meaning “flow”
• Most electronegative element
• Most reactive among the halogens
• Strongest oxidizing agent
• Essential element present in teeth
and bones in minimal quantities
• Used as anticariogenic agent
• Compounds:
➢ Fluorides – anticaries agent
a. Sodium fluoride (NaF) – for
dental prophylaxis
*dental fluorosis/mottled enamel –
excess fluoride consumed
COPPER
• Reddish-colored metal that
belongs in COINAGE metal group.
• 3rd most malleable metal
• excellent conductor of heat and
electricity
• 3rd best conductor of electricity
• essential trace element
• occurs in the respiratory pigment,
hemocyanin
• Hemocyanin – bluish pigment
found in the blood of some
arthropods and mollusks that
transports oxygen to tissues
PHARMACOLOGICAL ACTIONS
• essential to the metabolic process
• potential aid to iron assimilation
• enhances physiological utilization
of iron
• emesis (due to irritant action)
Wilson’s disease – a rare
hereditary disease resulting from
the inability to metabolize copper
leading to the deposition of toxic
amounts of copper in various
– tissues (e.g. eye, liver, brain,
kidney)
Treatment: Penicillamine
(Cuprimine) –promotes urinary
– excretion of excess copper
USES:
• Protein precipitant (astringent to
mucous membranes)
• Effective fungicide in minute
amounts
• Algaecide
• Bacteriostatic antiseptic
ZINC
• present in ores
➢ sphalerite or zinc blende (ZnS)
➢ smithsonite (ZnCO3)
• bluish-white metal
• when a zinc salt is heated with any
cobalt salt → cobalt zincate
(Rinmann’s green)
PHARMACOLOGICAL ACTIONS
• Present in highest concentrations
in testes, hair and nails, bone, and
pigmented tissues of the eye
• Present in carbonic anhydrase
(enzyme in blood cells that aids in
the transfer of carbon dioxide from
the tissues to the lungs)
 • Possesses emetic action and • Mucosal block – best known of the
strong local astringent action three hypotheses on iron absorption
when ingested • Ferritin – iron-carrying protein;
• Antidote for zinc poisoning: stores iron
NaHCO3 • Transferrin or siderophilin –
transports iron
CHROMIUM • Hemochromatosis – too much iron
• Group VIB transition metal builds up in the body
• A glucose tolerance factor – used
IRON PREPARATIONS
for improving blood sugar control
in diabetic people; acts as a • Ferrous salts are indicated for the
physiological enhancer of insulin treatment of “secondary anemias”.
activity, binding to insulin and • Secondary anemias are also
potentiating its action classified as “hypochromic
microcytic anemias” indicating a low
MANGANESE hemoglobin content and small size
• Essential trace element (traces cells.
occur in almost all organs of both ➢ Ferrous Sulfate
man and animals)  aka Green Vitriol,
• Cofactor involved in protein Copperas
synthesis, phosphorylation, and  stable form of iron
fatty acid & cholesterol synthesis  most economical and
• Possible synergistic action with most satisfactory form of
iron iron in the market
• Permanganates – powerful  hematinic (increases
oxidizing agents (0.02%-0.1% for blood hemoglobin)
urethral injections)  oxidizes readily on
• Used in the manufacture of glass, exposure to moist air
colored bricks, dryer in paints and forming crystals coated
varnishes with brownish-yellow
basic ferric sulfate
MOLYBDENUM
• Group VIB transition metal which COBALT
is a silvery-white, high-melting • Pure cobalt – pinkish-white metal
metal • Cobaltous salts – pink (hydrated);
• • Potentiates the uptake of iron in blue (anhydrous)
the body • Essential in the development of
• • A cofactor of several mammalian erythrocytes and hemoglobin (small
enzymes (sulfite oxidase, xanthine quantities)
dehydrogenase and aldehyde • Stimulates the bone marrow
oxidase) • Present in Vitamin B12
IRON (Cyanocobalamin)
• Used in the manufacture of beer
• It is an important constituent of the (stabilize foaming quality)
blood (hemoglobin) and oxidases • In the 1960s, some breweries added
(cytochrome oxidase) cobalt salts to beer to stabilize the
• absorption is enhanced with Vitamin foam (resulting in exposures of 0.04–
C 0.14 mg cobalt/kg).
• Hematite – most important source of • Cobalt (II) chloride or cobaltous
iron chloride (CoCl2) – aka Sympathetic
PHARMACOLOGICAL ACTIONS/USES ink or Lover’s ink; indicator in silica
gel beads
• Externally: Protein precipitant and
astringent (ferric salts)
• Internally: Formation of hemoglobin
 SAS 3 LECTURE NOTES KIDNEY – No urine production
INTESTINAL – Diarrhea
METAL TOXICITY/METAL POISONING –
is the toxic effect of certain forms and does • Elements in groups IB, IIB, IIIA, IV
on life. in rows six and seven – which are
referred as HEAVY METALS are
• Some metals are toxic when they form
usually have greater potential to
POISONOUS SOLUBLE COMPOUND.
INDUCE TOXICITY.
• Definition of toxic metals includes at
least the following: METALS – are measured in biological
➢ Thallium fluids using:
➢ Cadmium
➢ Atomic absorption
➢ Manganese
spectrometry with flame (AAS-
➢ Lead
F)
➢ Mercury
➢ Electrothermal atomization
➢ Radioactive Metals
furnace (AAS-ETA)
RADIOACTIVE METALS – have both ➢ Inductively coupled plasma-
radiological and chemical toxicity. optical emission spectrometry
(ICP-OES)
• METALS in an oxidation state ➢ Inductively coupled plasma-
abnormal to the body may also become mass spectrometry (ICP-MS)
toxic ➢ High performance liquid
• CHROMIUM (III) is an essential trace chromatography-mass
element spectrometry (LC-MS)
• Whereas CHROMIUM (VI) is a
carcinogen PHOTOMETRIC ASSAYS – are
also possible but require large
HEAVY METALS – are dangerous because volumes of a sample and have
they tend to bioaccumulate limited analytical performance
BIOACCUMULATION – means an increase CHELATION THERAPY – an
in the concentration of a chemical in a option for treatment of metal
biological organism over time, compared to poisoning
the chemical’s composition in the
environment. BERYLLIUM

PHYSIOLOGIC EFFECT OF SOME • ALKALINE EARTH METALS

METAL INTOXICATION together with Mg, Ca, Sr, Ba and
Ra
SYSTEMATIC ➢ Magnesium, Calcium,
➢ Chills Strontium, Barium, and
➢ Fever Radium)
➢ Pain • Called GLUCINUM because of the
sweet taste of its salts.
EYE – Yellowing • Differentiated from magnesium by
MOUTH - Metallic taste adding quinalizarin + bromine
water
MUSCULAR - Weakness ➢ Be: PERSISTENCE of blue
LIVER – Decreased function color
➢ Mg: DISAPPERANCE of blue
SKIN – Yellowing color
CIRCULATORY – Anemic/Shock MOST TOXIC METAL
➢ Inhibits carbohydrate metabolic
GASTRIC cycle by preventing breakdown of
➢ Vomiting phosphorus compounds
➢ Nausea ➢ Disturbs respiration,
➢ Abdominal pain circulation, and temperature
➢ Burning sensation ➢ No specific antidote is known
• Never used in medicine • It may inhibit potassium flux across
• Used in the fluorescent lighting industry biologic membranes by binding to Na-K
• Metallic, Alloys and ceramics of Be are ATP transport enzymes
widely used in dental appliances, • Primarily use as RODENTICIDE
wheelchairs, nuclear power and neutron
CLINICAL PRESENTATION
modulator.
• Chronic Beryllium disease (CBD) is a ACUTE EFFECTS CHRONIC EFFECTS
CHRONIC RESPIRATORY CONDITION ❖ Abdominal ❖ Painful
due to CHRONIC BERYLLIUM exposure pain, nausea, peripheral
that is characterized by the formation of vomiting, and neuropathy,
GRANULOMAS resulting from immune diarrhea myopathy,
reaction to Be in the lungs. (sometimes with chorea,
hemorrhage) stomatitis and
ALUMINUM
❖ Shock may ophthalmoplegia
• MOST ABUNDANT METAL & 3rd result from ❖ Hair loss and
MOST ABUNDANT ELEMENT massive fluid of nail dystrophy
blood loss (mees’ lines)
PHARMACOLOGICAL ACTIONS ❖ Within 2-3 days, may appear
delirium, after 2 – 4
• may constrict the blood vessels when seizures, weeks.
applied topically respiratory
• astringent (inherent) failure and
• antiseptic death may
• antiperspirant occur
DIAGNOSIS
ALUMINUM POWDER – used as an
inhalation in the treatment of SILICOSIS SPECIFIC LEVELS OTHER USEFUL
LABORATORY
ALUMINUM FOIL - used in burn STUDIES
treatment; protects the burn/ conserves ❖ URINARY ❖ CBC
fluid/ stimulates the tissue growth THALLIUM ❖ ELECTROLYTES
normally less ❖ GLUCOSE
LOW PARATHYROID HORMONE (PTH) - - than 0.8mcg/L. ❖ BLOOD UREA
Aluminum overload may replace calcium in Concentrations NITROGEN
bone disrupting normal osteoid formation higher than 20 (BUN)
and may be reflected diagnostically with mcg/L provide ❖ CREATININE
low parathyroid hormone (PTH). evidence of ❖ HEPATIC
excessive TRANSMINASES
exposure and
THALLIUM may be (Since thallium is a
associated with RADIOPLAQUES,
• It is a soft metal that quickly oxidizes subclinical plain abdominal x-
upon exposure to air. It is a minor toxicity during rays may be useful
workplace after ACUTE
constituent in a variety of ores. exposures. INGESTION.
➢ Ores is a natural or sediment rock ❖ BLOOD
• Thallium salt used in the manufacture THALLIUM
of jewelry, semiconductors, and optical LEVELS are not
devices. considered
reliable measures
• From thallos meaning “green twig” of exposure
• This can also be a by-product of lead except after large
smelting which can be very toxic. exposures.
❖ HAIR LEVELS
MECHANISM TOXICITY are of limited
value, used
• It is not known mainly in
• It appears to affect a variety of enzyme documenting past
systems resulting in GENERALIZED exposure and in
CELLULAR POISONING forensic cases.
TREATMENT • It is a metal commonly found in the
environment (eg. Ceramics at home,
• Emergency and supportive measures
paint, leaded gasoline, water pipes
• Specific drugs and antidotes
soldered with lead, soil)
➢ Prussian blue (ferric ferrocyanide)
• Absorption is slow but action is
➢ Activated charcoal
cumulative; accumulates and stored in
➢ BAL (Dimercaprol)
bones.it can be ingested, inhaled or
• Decontamination
through dermal contact.
➢ Gastric lavage – consider for large
• Toxicity will result to impaired growth
recent ingestions
and mental development, decrease
• Enhanced elimination
vitamin D and hemoglobin synthesis,
SILICON nephropathy, encephalopathy and
death
• The 2nd MOST ABUNDANT ELEMENT ANTIDOTE
next to oxygen ➢ Chelation of BAL
COMPOUNDS OF SILICON ➢ Dimercaprol

• COLLOIDAL SILICON DIOXIDE MECHANISM TOXICITY

➢ Used as adsorbent, desiccant, • The multisystem toxicity of lead is
thickener mediated by several mechanisms,
• AMORPHOUS OXIDE OF SILICON including inactivation or alteration of
➢ Inhalation of asbestos enzymes and other macromolecules
➢ Containing dust leads asbestosis, by binding to sulfhydryl, phosphate,
deposition of asbestos fiber in the or carboxyl ligands and interaction
pulmonary alveoli with essential cations, most notably
➢ Example: Asbestos calcium, zinc, and iron. Pathologic
• METHYLATED POLYMERS OF alterations in cellular and
SILICON mitochondrial membranes,
➢ Silicon implants have come to neurotransmitter synthesis and
public attention. function, heme synthesis, cellular
➢ Silicon appears to induce a redox status, and nucleotide
response from polymorphonuclear metabolism may occur.
cells and macrophages that bind • Pharmacokinetics. Inhalation of lead
small particles of silicon and fume or other fine, soluble
transport them to lymph nodes particulate results in rapid and
where they can accumulate. extensive pulmonary absorption, the
➢ Example: Silicone major though not exclusive route of
SILICOSIS – a lung condition resembling exposure in industry.
CHRONIC TUBERCOLOSIS TOXIC DOSE
LEAD ➢ Dermal absorption
• It is a soft, malleable metal that is ➢ Ingestion
obtained chiefly by the primary smelting ➢ Inhalation
and refining of natural ores or by the TREATMENT
widespread practice of recycling and
secondary smelting of scrap lead • Emergency and supportive measures
products • Specific drugs and antidotes.
• Lead is used for weights and radiation ➢ Encephalopathy
shielding, and lead alloys are used in the ➢ Symptomatic
manufacture of pipes; cable sheathing; ➢ Asymptomatic children with
brass, bronze, and steel; ammunition; elevated blood lead levels
and solder (predominantly electrical ➢ Asymptomatic adults
devices and automotive radiators). ➢ Blood lead monitoring during
• Lead compounds are added as chelation
pigments, stabilizers, or binders in
paints, ceramics, glass, and plastic
 SILVER PHARMACOLOGICAL ACTIONS
• Protoplasmic poison
• Also called noble metal because of its
• Effective in polycythemia vera
use in making articles of value (e.g.,
(represses the bone marrow which
coins, ornaments, jewelry)
overproduces RBC)
• May be precipitated by HCl
• Was once used as antisyphilitic agent
PHARMACOLOGICAL ACTIONS and still currently present in some
insecticides.
• Protein precipitant
ANTIDOTES
• Antiseptic, astringent, and corrosive to
• Freshly prepared Iron (III) and
tissues
Magnesium hydroxide (if still in the GI
• Possesses oligodynamic action tract)
• Treatment of burn (silver sulfadiazine) • Dimercaprol (aka 2,3-
TOXICITY dimercaptopropanol, British Anti-
Lewisite or BAL) via IM injection
• Discolors skin (argyria) which may SPECIAL TEST TO DETERMINE THE
result to growth retardation, PRESENCE OF ARSENIC
hemopoiesis, cardiac enlargement, ➢ Gutzeit test
degeneration of the liver, destruction of ➢ Marsh test
renal tubules. ➢ Reinsch test
ANTIDOTE ANTIMONY
• 6% Na2S2O3 + 1% K4Fe (CN)6 • Is widely used as a hardening agent
subcutaneously but requires several in soft metal alloys and alloys of lead;
injections into the affected area for compounding rubber; as a major
ARSENIC flame-retardant component of
plastics and as a coloring agent in
• Steel-gray brittle solid with a distinct dyes and varnishes, paints and
metallic luster glazes.
• It is widely known to be toxin that • Compared to arsenic, it is less readily
gained notoriety from its extensive use absorbed and produces topical
by Renaissance and was known as irritation
Poison of Kings and King of Poisons. • More caustic to the skin than arsenic
• It is listed as number one toxicant in causing papular eruptions which
US. develop into vesicular and pustular
• It is also a known carcinogenic agent sores
MECHANISM OF TOXICITY • Exhibits expectorant and nauseant
action orally in small quantities
• Arsenic compounds may be organic or • Exposure to Sb dust over a period of
inorganic and may contain arsenic in years leads to pneumoconiosis; It
either a: may also cause cardiac arrhythmias,
➢ pentavalent (arsenate) spontaneous abortion, and
➢ trivalent (arsenite) dermatitis and inability of the blood
• Arsenicals exert their toxic effects to clot.
through multiple mechanisms, MECHANISM OF TOXICITY
including inhibition of enzymatic • Compounds of probably act by
reactions vital to cellular metabolism, binding to sulfhydryl groups,
induction of oxidative stress, and enhancing oxidative stress, and
alteration in gene expression and cell inactivating key enzymes.
signal transduction • Ingested antimonial are also
• Arsenite and arsenate undergo in vivo corrosive to mucosal membranes.
biotransformation to less toxic
pentavalent monomethyl and dimethyl CLINICAL PRESENTATION
forms, there is evidence that the • Acute ingestion of antimony causes
process also forms more toxic trivalent nausea, vomiting, hemorrhagic
methylated compounds. gastritis, and diarrhea
 ("cholerastibie"). Hepatitis and renal
insufficiency may occur. Death is
rare if the patient survives the initial
gastroenteritis. Cardiac
dysrhythmias (including torsade),
pancreatitis, and arthralgias have
been associated with the use of the
organic antimonial compounds for
treatment of parasitic infections (e.g.,
leishmaniasis).
• Chronic exposure to antimony dust
and fumes in the workplace is the
most common type of exposure and
may result in headache, anorexia,
pneumonitis, peptic ulcers, and
dermatitis (antimony spots). Sudden
death presumably resulting from a
direct cardiotoxic effect has been
reported in workers exposed to
antimony trisulfide. Based on
evidence of in vitro genotoxicity and
limited rodent carcinogenicity
testing, antimony trioxide is a
suspected carcinogen.
TREATMENT
• Large-volume intravenous fluid
resuscitation may be necessary for
shock caused by gastroenteritis (see
Hypotension). Electrolyte
abnormalities should be corrected,
and intensive supportive care may be
necessary with multiple organ failure.
OFFICIAL COMPOUND
• Antimony potassium tartrate
(KSbOC4H4O6)
➢ aka Tartar Emetic
➢ formerly used as emetic and
expectorant
➢ used as anti-schistosomal
agent (IV)
CADMIUM
• It is found in sulfide ores, along with
zinc and lead. Exposure is common
during the mining and smelting of
zinc, copper, and lead.
• The metallic form of Cd is used in
electroplating because of its
anticorrosive properties, the metallic
salts are used as pigments and
stabilizers in plastics, and Cd alloys
are used in soldering and welding and
in nickel-cadmium batteries. Cd
solder in water pipes and Cd pigments
in pottery can be sources of
contamination of water and acidic
foods.
• It is a member of volatile metal group
MECHANISM OF TOXICITY
• Inhaled Cd is at least 60 times more
toxic than the ingested form.
• Fumes and dust may cause delayed
chemical pneumonitis and resultant
pulmonary edema and hemorrhage.
• Cd is a known human carcinogen
(IARC Group 1).
• Ingested Cd is a GI tract irritant.
Once absorbed, Cd is bound to
metallothionein and filtered by the
kidney, where renal tubule damage
may occur.
ITAI-ITAI DISEASE
• Also known as the “ouch-ouch
disease”
• First documented occurrence of mass
cadmium poisoning in the world due
to mining in Toyama Prefecture;
contracted from drinking water and
eating rice contaminated with
cadmium
SYMPTOMS
➢ Weak and brittle bones
➢ Spinal and leg pain
➢ Anemia
➢ Kidney failure
TREATMENT
• Emergency and supportive measures
➢ Inhalation
➢ Ingestion
• Specific drugs and antidotes
➢ There is no evidence that
chelation therapy (eg, with
BAL, EDTA, or penicillamine)
is effective, although various
chelating agents have been
used
PHARMACOLOGICAL ACTIONS
• Closely resembles zinc in action but
is more toxic
• Behaves like mercury systemically
and after absorption, produces death
by arresting respiration; -its toxicity
results to renal dysfunction with
proteinuria with slow onset.
 MERCURY
• It is a naturally occurring metal that
is mined chiefly as HgS in cinnabar
ore. It is converted to three primary
forms, each with a distinct toxicology:
elemental (metallic) mercury (Hgo),
inorganic mercury salts (eg, mercuric
chloride [HgCl2]), and organic (alkyl
and aryl) mercury
(eg,methylmercury).
• Also called liquid silver or quicksilver
with low boiling point and melting
point
• Cinnabar (HgS) is a mineral source of
mercury; aka Aethrop’s mineral
• Mercury that falls into cracks and
difficult to clean places is removed
best by covering with powdered
sulfur, allowing several days to for
conversion to sulfide then vacuumed.
• Elemental mercury (Hg 0) can be
converted chemically or biologically to
its toxic form (Hg +,2+) and or the
methylated or alkyl Hg which will
result kidney failure.
• Mercury and its compounds are
inherently toxic
MECHANISM OF TOXICITY
• Mercury reacts with sulfhydryl (SH)
groups, resulting in enzyme inhibition
and pathologic alteration of cellular
membranes.
• Elemental mercury and
methylmercury are particularly toxic
to the CNS. Metallic mercury vapour
is also a pulmonary irritant.
Methylmercury is associated with
neurodevelopmental disorders.
• Inorganic mercuric salts are corrosive
to the skin, eyes, and GI tract and are
nephrotoxic.
• Inorganic and organic mercury
compounds may cause contact
dermatitis.
MINAMATA DISEASE
• Acquired through ingestion of
contaminated fish, shellfish and sea
mammals in Minamata Bay, Japan
SYMPTOMS OF POISONING
• Initial: burning metallic taste, thirst,
sore throat, visual field constriction,
hearing loss,
• Latter: salivation, sore gums, bloody
diarrhea, severe gastric pain, and
cerebral cortex necrosis.
ANTIDOTES
• Egg white or milk
➢ to inactivate mercury ions by
coagulation followed by extensive
gastric lavage
• Sodium formaldehyde sulfoxylate
➢ for the bichloride
• Dimercaprol
➢ agent of choice; given via IM or
Penicillamine that would
mobilize and excrete Hg in the
urine
MERCURY THERAPEUTIC USES
• Diuretic – mercurial diuretics bring
about sodium and water diuresis by
inhibiting the reabsorption of sodium
• Antiseptic – mercuric ion is a protein
precipitant
• Antisyphilitic – mercury and its salts
have been used in the prophylaxis
and treatment of syphilis (Calomel
ointment)
• Cathartic
• Parasiticide and fungicide – used
in the treatment of impetigo and
ringworm infections in the form of
Ammoniated
• Mercury Ointment
NICKEL
• It is was once known as “Old Nick’s
copper” or “Kupfernickel”
• It is use favorably as alloying metal
(eg. jewelry) due to its anticorrosive
and hardness property.
• It can be used in nickel-based
batteries, catalyst in the
hydrogenation of oil.
ALLOY
• Raney Nickel – nickel-aluminum alloy
• German Silver – nickel, zinc, and
copper alloy
• Nickel carbonyl (Ni[CO]4) – used in
pertroleum refining is the most toxic
chemical known to humans.
• Exposure and toxicity may cause
contact dermatitis, pulmonary
congestion, inability to oxygenate
hemoglobin especially if lesion in
present in liver, kidney, adrenal
gland, and speen.
 SAS 4 LECTURE NOTES COLLIGATIVE PROPERTIES OF A
SOLUTION
IMPORTANCE OF PH AND BUFFER
• Directly related to the total
SYSTEMS IN ANALYTICAL CHEMISTRY
number of solute particles per
• Many chemical reactions upon which an mass of solvent
analytical procedure is based require ➢ VAPOR PRESSURE LOWERING
optimum pH conditions for the reaction ➢ BOILING POINT ELEVATION
to proceed to completion. ➢ FREEZING POINT
• Analysis based on neutralization DEPRESSION
reactions the pH of the solution at the ➢ INCREASED OSMOTIC
equivalence point determines which PRESSURE
indicator is to be used for analytical
OSMOTIC PRESSURE
determination
pH • Most important colligative
• The measurement of the alkalinity and property
the acidity of a product or a substance. • Biological systems are made of
• The pH value of a solution reflects the different membranes which
relative concentration of hydrogen ions vary in pore size thus has
(H+) or protons to the concentration of different ability to select
hydroxide ions (OH-) in a solution molecules of different size and
• Dictates on how a specific drug product shape.
is absorbed in our system • Differences in the
• Acidic drug substances are absorbed in concentrations of osmotically
the stomach thus if the drug product is active molecules that are
desired to be absorbed on that site, drug unable to cross a membrane
company must design the product to move to establish an osmotic
become acidic. equilibrium.
• pH also is considered in products for the • Osmotic pressure generally
parenteral preparations. pH governs the movement of
computation and adjustment is needed solvent (water in biological
for this type of delivery system. pH systems) across membranes
computation and adjustment is needed that separate two solutions.
for this type of delivery system.
• Cells must maintain a constant pH so
that the enzymes and processes taking
place inside the cells will continue as
needed. Chemical and enzymatic
reactions are typically dependent on a
specific pH range. Thus, it is important
to understand pH and be able to
determine the pH of various solutions
SORENSEN PH SCALE OSMOTIC PRESSURE IS
EXPRESSED THROUGH:
• Osmolality: expresses
concentrations relative to
mass of the solvent (1
Osmol/kg H2O)
• Osmolarity: expresses
concentrations per volume of
solution (1 Osmol/L solution).
• Osmolality is what the
clinical laboratory measures.
OSMOMETRY - The technique used for plasma. The partial pressure of a gas in
measuring the concentration of solute a gas mixture is defined as the
particles that contribute to the osmotic substance fraction of gas (mole fraction)
pressure of the solution times the total pressure.
ARTERIAL BLOOD GAS (ABG) TEST
FREEZING POINT DEPRESSION
• An arterial blood gas (ABG) test is a
• Another colligative property that can be blood test that requires a sample from
also used commonly for the an artery in your body to measure the
measurement of osmolality in clinical levels of oxygen and carbon dioxide in
laboratory. your blood.
• Simple to use. • Arterial blood gas tests can help
• Freezing point depression, unlike vapor healthcare providers interpret
pressure is dependent of the changes in conditions that affect your respiratory
ambient temperature. system, circulatory system and
metabolic processes (how your body
VAPOR PRESSURE OSMOMETER transforms the food you eat into energy),
• Related directly not to a change in vapor especially in emergency situations.
pressure (in millimetres of mercury) but • In blood gas work, the standard
to the decrease in dew point measurements of partial pressure are
temperature of the pure solvent (water) always made at Body Temperature
caused by the decrease in vapor (usually 37 °C), at P(Amb/ Atmospheric
pressure of the solvent by the solutes Barometric Pressure),and in the
presence of Saturated water vapor (SVP)
VAPOR PRESSURE OSMOMETER vs. the PH2O = 47 mm Hg
FREESING POINT DEPRESSION
OSMOMETER
• An important clinical difference between
the vapor pressure technique and the
freezing point depression osmometer is
the failure of the former to include in its
measurement of total osmolality any
volatile solutes present in the serum
thus use of this type of osmometer is not
recommended or most clinical
laboratories.
BLOOD GAS
• Blood gases are a measurement of how
much oxygen and carbon dioxide are in
your blood. They also determine the
acidity (pH) of your blood.
• Clinical management of respiratory and
metabolic disorders depends on rapid,
accurate measurements of oxygen and
carbon dioxide gas in blood.
• Determination of blood gases also plays
an important part in the detection of
acid base imbalances.
• The partial pressure (tension) of a gas
dissolved in blood is equal to the partial
pressure of the gas in an imaginary ideal
gas phase in equilibrium with the blood.
At equilibrium, the partial pressure of a
gas is the same in erythrocytes and
plasma, so that the partial pressure of a
gas is the same in whole blood and
DIFFERENT GAS LAWS
• Boyle’s law
➢ The volume of an ideal gas at a
constant temperature varies
inversely with the pressure exerted
to contain it.
• Charles’ (Gay-Lussac’s) law
➢ The volume of an ideal gas at a
constant pressure varies directly
with its absolute temperature.
• Avogadro’s hypothesis
➢ Equal volumes of different ideal
gases at the same temperature and
pressure contain the same number
of molecules.
• Dalton’s law
➢ The total pressure exerted by a
mixture of ideal gases is the sum of
the partial pressure of each of the
gases in the mixture.
• Henry’s law
➢ The amount of a sparingly soluble
gas dissolved in a liquid is
proportional to the partial pressure
of the gas over the liquid.
BICARBONATE
• Total Carbon Dioxide
• Colorless and harmless gas.
• Respiratory stimulant usually with
507% oxygen.
• Total carbon dioxide is measured in the
clinical laboratory by
➢ (1) acidification of a serum or plasma
sample and measurement of carbon
dioxide released by the process
➢ (2) alkalinisation and measurement
of total bicarbonate.
• Methods used or total CO2
measurement:
➢ (1) indirect electrode-based
methods: the amount of released
gaseous CO2 after acidification is
determined by a PCO2 electrode.
➢ (2) enzymatic methods or CO2: the
specimen is first alkalinized to
convert all CO2 and carbonic acid to
HCO3 –
OXYGEN IN BLOOD
• The total O2 content (ctO2 or
concentration of total oxygen gas) of a
blood sample is the sum of the
concentrations of hemoglobin-bound O2
and of dissolved O2.
• At a blood ctO2 of 9 mmol/L, the O2
associated with hemoglobin as
oxyhemoglobin (O2Hb or oxygen gas in
hemoglobin) is 8.86 mmol/L. The O2Hb
is defined as erythrocyte hemoglobin
with O2 reversibly bound to Fe2+ of its
heme group. Each mole of haemoglobin
-Fe2+ binds 1 mol of O2.
• The affinity of hemoglobin for O2 may
depends on the following actors: (1)
temperature, (2) pH, (3) PCO2, (4)
concentration of 2,3-diphosphoglycerol
(2,3-DPG).
PULSE OXIMETER - commonly use to
continuously monitor saturation factor
of oxygen in haemoglobin (SO2Hg)
because it is more reliable.
TRANSCUTANEOUS MONITORING -
PCO2 and PO2 is a noninvasive
continuous monitoring approach that
has particular value and general
success especially in neonatal and
pediatric care
ACID – BASE PHYSIOLOGY
• The normal human diet is almost
neutral.
• Metabolic process in the body result in
the production of relatively large
amounts of carbonic acid, phosphoric
acid, and other acids.
• Acid-base balance involves in an
accounting of the carbonic acid (H2CO3,
HCO3, CO3 and CO2) and non-carbonic
acids and conjugate bases in terms of
input (intake plus metabolic production)
and output (excretion plus metabolic
conversion) over a given period of time.
• Acidemia (Acidosis) is defined as an
arterial blood pH <7.35 and alkalemia
(Alkalosis) indicates an arterial blood pH
>7.45.
• Acid-base balance is the homeostatic
maintenance of acids and bases within
the body to achieve a physiological pH of
approximately 7.40.
THE STEPS IN ACID EXCREATION IN
THE KIDNEY ARE AS FOLLOWS:
1. Through glomerular filtration,
sodium salts of mineral and organic
acids are removed from the plasma.
2. Once transferred from the renal
filtrate or tubular fluid, sodium
reacts in the tubule cells with
carbonic acid formed by the
carbonic anhydrase-catalyzed
reaction of carbon dioxide and water
 in a chemical process called the
sodium-hydrogen exchange: Na +
H2CO3 NaHCO3 + H
3. The sodium bicarbonate then return
to the plasma, having excreted from
the lungs as CO2, now the protons
enter the tubular fluids, forming
acids of the anions of the sodium
salts.
• Many pathological conditions are
accompanied by acid –base and
electrolyte disturbances in the blood.
Abnormalities in acid-base status of the
blood are always accompanied by
characteristic changes in electrolyte
concentrations in the plasma. Hydrogen
ions cannot accumulate without
concomitant accumulation of anions
(such as, Cl− or lactate), or without
exchange or cations (such as, K+ or Na+)
SODIUM
• Disorders of Na+ homeostasis can occur
because of excessive loss, gain or
retention of Na+ or because of excessive
loss, gain, or retention of H2O.
• When kidneys are hypoperfused (when
renal volume decreases), the distal
tubules, under the influence of
aldosterone reclaim Na+
• Water regulation in the kidney occurs
from the distal tubule through the
collection duct where tubular
permeability to H2O is under the
influence of antidiuretic hormone
(ADH).
• The body’s mechanism for restoring Na+
/H2O homeostasis is H2O.
POTASSIUM
• Disturbances in potassium homeostasis
has serious consequences.
• Hypokalemia is associated with serious
neuromuscular symptoms, tachycardia
that may lead to cardiac arrest.
• Hyperkalemia causes mental
confusion, flaccid paralysis of the
extremities, bradycardia, severe
vascular collapse, and cardiac arrest.
CHLORIDE
• In the absence of acid -base
disturbances, Cl− concentrations in
plasma generally will follow those of
Na+. In respiratory acidosis, it is
accompanied by increase HCO− 3, is
another common cause of decrease Cl−
with normal Na+.
• Increase plasma Cl− concentration,
similar to increase Na+ concentration,
occurs with dehydration, prolonged
diarrhea with loss of sodium
bicarbonate, and overtreatment with
normal saline solutions, which have a
Cl− content of 154 mmol/L. It may also
be seen in respiratory alkalosis because
of renal compensation for excreting
HCO−3
BIOCARBONATE
• The total carbon dioxide (CO2) content
of plasma consists of carbon dioxide
dissolve in an aqueous solution (CO2),
CO3 loosely bound to amine groups in
proteins (carbamine compounds), HCO3
−, and very small quantities of CO3 2 −
ions and carbonic acid (H2CO3).
• Acid-base disturbances are traditionally
classified as
➢ metabolic acidosis
➢ metabolic alkalosis,
➢ respiratory acidosis
➢ respiratory alkalosis
• Acidosis only occurs as the result of one
(or a combination) of three mechanisms:
➢ increase addition of acid
➢ decrease elimination of acid
➢ increased loss of base
• Alkalosis occurs only by
➢ increase addition of base
➢ decreased elimination of base
➢ increased loss of acid.
CONDITIONS RESULTING TO
METABOLIC ACIDOSIS
1. Methanol ingestion
2. Renal failure
3. Diabetes (Ketoacidosis)
4. Paraldehyde Toxicity
5. Ischemia
6. Lactic acidosis
7. Ethylene glycol ingestion
8. Salicylate intoxication
9. Diarrhea (severe)
 CONDITIONS RESULTING TO
METABOLIC ALKALOSIS
1. Prolonged vomiting
2. Upper duodenal obstruction
3. Prolonged diuretic therapy (loop
diuretic)
4. Cystic fibrosis
5. Mineralocorticoid (primary
secondary hyperaldosteronism,
Bilateral adrenal hyperplasia,
6. Glucocorticoid excess (Primary adrenal
adenoma or Cushing syndrome and
disease, exogenous cortisol therapy,
excessive licorice ingestion, Barterr
syndrome
7. High doses of bicarbonate, sodium
citrate, antacids, carbenicillin
penicillin
CONDITIONS RESULTING TO
RESPIRATORY ACIDOSIS
1. Overdose of narcotics and barbiturates
2. Central nervous system trauma,
tremors and degenerative disorders
3. Infection in the CNS (encephalitis and
meningitis)
4. Comatose patient secondary
cerebrovascular accident caused by
intracranial hemorrhage
5. Chronic obstructive disease
6. Pulmonary fibrosis
7. Status asthmaticus (severe)
8. Pulmonary infection
9. Neurological disorders affecting the
muscles in respiration
10. Abdominal distention as
peritonitis and ascites
11. Extreme obesity
12. Sleep apnea
FACTORS CAUSING RESPIRATORY
ALKALOSIS
1. Anxiety
2. Gram-negative septicemia
3. Metabolic encephalopathy
4. Meningitis and Encephalitis
5. Intracranial surgery
6. Severe anemia leading to hypoxia
7. Overuse of salicylates, catecholamines
and progesterone (increase progesterone
esp. in 3rd trimester)
8. Hyperthyroidism
9. Pneumonia
10. Asthma
11. Pulmonary emboli
12. Congestive heart failure
APPLICATION OF HENDERSON -
HASSELBALCH EQUATION
• Acids: donate protons (H+ ions) in
solution
• Bases: accept protons.
• The pH of the solution is defined as the
negative logarithm of the hydrogen ion
and activity (pH= -log aH+).
• The pK is the pH at which an acid is half
dissociated, existing as equal
proportions of acid and conjugate base.
Thus, acids have pK values <7.0,
whereas bases have pK values >7.0.
• The lower the pK, the stronger the acid
is, and the higher the pK, the stronger
the conjugate base is.
or • The pH of plasma may be considered to
be a function of two independent
variables:
➢ (1) the PCO2, which is regulate by
the lungs an represents the acid
component of the carbonic
acid/bicarbonate buffer system
➢ (2) the concentration of titratable
base which is regulate by the
to kidneys.
• Acid-base balance or actual bicarbonate
is not measured but rather calculated
using Henderson- Hasselbalch
equation.
• In 1916. Hasselbalch showed a
logarithmic equation that adopted today
as:
in
• When pK and α for a normal plasma at
37oC are inserted, the equation will take
as follows:
 BUFFER SYSTEMS SAS 5 LECTURE NOTES
• A buffer is a mixture of a weak acid and QUALITATIVE QUANTITATIVE
a salt of its conjugate base that resists ANALYSIS ANALYSIS
changes in pH when a strong acid or ➢ establishes ➢ determines the
base is added to the solution. the chemical relative
• Generally, buffers work best at resisting identity of the amount of
pH changes in the interval ±1 pH unit of species in the these species
its pK, (buffers work best when the ratio sample or analytes, in
numerical
of acid /base is within the range of 10:1
terms.
to 1:10).
• Buffers are also more effective at higher
• We can compute the results of a typical
concentrations
quantitative analysis from two
Efficient buffer systems utilized by the body measurements:
to maintain pH are found in: ➢ Mass of the volume of a sample
being analyzed.
1. Bicarbonate/Carbonic acid (HCO3 /
➢ Some quantity that is
H2CO3), in the plasma and kidneys;
proportional to the amount of
➢ It is the most buffer of plasma. Normal
analyte in the sample such as
bicarbonate/d CO2 ratio is 20:1. The
mass, volume, intensity of light
effectiveness of the bicarbonate buffer is
or electrical charge.
based on the fact that the lungs are able
to readily dispose of or retain CO2 while NOTE: This second measurement
the renal tubules are able to increase or usually completes the analysis, and
decrease the rate of reclamation of we usually classify analytical
bicarbonate from the glomerular filtrate. methods according to the nature of
2. Phosphate Buffer [Monohydrogen this final measurement.
phosphate/dihydrogen phosphate
• GRAVIMETRIC METHOD - determines
(HPO4/H2PO4)], in the cells and
the mass of the analyte or some
kidneys.
compound chemically related to it.
➢ The total concentration of this buffer in
both erythrocytes and plasma accounts • VOLUMETRIC METHOD - measures
for about 5% of the nonbicarbonate the volume of a solution containing
buffer value of plasma. Organic sufficient reagent to react completely
phosphate (2,3-diphosphoglycerate) with the analyte.
present in erythrocytes, accounts for • ELECTROANALYTICAL METHOD -
about 16% of the nonbicarbonate buffer measures electrical properties such as
value of erythrocytes. potential, current, resistance, and
3. Plasma Protein and Hemoglobin Buffer quantity of electrical charge
➢ Hemoglobin and proteins (esp. • SPECTROSCOPIC METHOD - explores
albumin), account for the greatest the interaction between
portion (>90%) of the non-bicarbonate electromagnetic radiation and analyte
buffer value of plasma. It is the most atoms or molecules or the emission of
effective system for buffering the radiation by analytes
carbonic acid produced during SI UNITS
metabolic processes. • Scientists throughout the world have
adopted a standardized system of units
known as the International System of
Units (SI).
• This system is based on the seven
fundamental base units shown in the
table.
• Numerous other useful units, such as
volts, hertz, coulombs, and joules, are
derived from these base units.
• To express small or large measured particles, or specified groups of such
quantities in terms of a few simple particles as represented by a chemical
digits, prefixes are used with these base formula.
units and other derived units. • It is the amount of the specified
substance that contains the same
number of particles as the number of
carbon atoms in exactly 12 grams of
12C.
• Avogadro’s number NA 5 6.022 3
1023.
• The molar mass M of a substance is
the mass in grams of 1 mole of that
substance.
IMPORTANCE OF SI UNITS IN • We calculate molar masses by
ANALYTICAL CHEMISTRY summing the atomic masses of all the
• In determining the amount of chemical atoms appearing in a chemical
species from mass measurements formula.
metric units of kilograms (kg), grams SOLUTIONS AND THEIR
(g), milligrams (mg), or micrograms (μg) CONCENTRATIONS
are used. • MOLARITY (M)
• Volumes of liquids are measured in ➢ Molarity = moles of solute/liters
units of liters (L), milliliters (mL), of solution
microliters (μL), and sometimes ➢ Measurement of the moles in the
nanoliters (nL). total volume of the solution
• The liter, the SI unit of volume, is • MOLALITY (m)
defined as exactly 1023 m3. The ➢ molality = moles of
milliliter is defined as 1026 m3, or 1 solute/kilograms of solvent
cm3. ➢ Measurement of the moles in
relationship to the mass of the
MASS WEIGHT solvent.
 Mass is an  Weight is the • NORMALITY (N)
invariant force of ➢ Normality = number of mole
measure of the attraction equivalents/1 L of solution
quantity of between an ➢ Like molarity, normality relates
matter in an object and its the amount of solute to the total
object. surroundings,
volume of solution; however,
principally the
normality is specifically used for
earth.
acids and bases.
 Mass is how  Weight is a force
much matter exerted on a • When water is the solvent and the
an object mass by a concentration of the solution is low,
contains gravity these differences can be negligible (d =
 Mass is a  Weight is not a 1.00 g/mL). However, when the
constant for a constant. It density of the solvent is significantly
body and does changes from different than 1 or the concentration of
not change with place to place. the solution is high, these changes
location become much more evident.
 The kilogram is  The Newton is a • Example: Compare the molar and
a unit of mass unit of weight molal volumes of 1 mol of a solute
MOLE dissolved in CCl4 (d = 1.59/mL).
• For a 1 Molar solution, 1 mol of solute
• Abbreviated as ‘mol’
is dissolved in CCl4 until the final
• SI unit for the amount of a chemical
volume of solution is 1 L.
substance
• For a 1 molal solution, 1 mol of solute
• Always associated with specific
is dissolved in 1 kg of CCl4.1 kg
microscopic entities such as atoms,
of CCl4 × (1,000 g/1 kg) × (mL/1.59 g)
molecules, ions, electrons, other
= 629 mL CCl4