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Analytical Toxicology. Methodology of toxicological analysis.
Chemicotoxicological analysis of inorganic acids, alkalis, nitrates
and nitrites
Topic of the lecture:
NATIONAL UNIVERSITY OF PHARMACY
DRUG AND ANALYTICAL TOXICOLOGY DEPARTMENT
DRUG AND ANALITICAL TOXICOLOGY
Lecturer: Karpushyna Svitlana Anatoliivna,
Ass. Prof., PhD in Chemistry
National University of PharmacyDrug and Analytical Toxicology Department
Plan of the lecture
1. Subject and applied aspects of Analytical Toxicology.
2. Methodology of toxicological analysis.
3. Chemicotoxicological analysis of inorganic acids, alkalis, nitrates and nitrites.
3.1. Physicochemical properties and usage of mineral acids, alkalis, nitrates and nitrites.
Toxicity of mineral acids, alkalies, nitrite.
3.2. The general scheme of chemical toxicological examination of biological material for
mineral acids, alkalis, nitrates and nitrites.
3.3. Analysis of the dialyzate for sulphuric, nitric and hydrochloric acids.
3.4. Analysis of the dialyzate for potassium hydroxide, sodium hydroxide and ammonium
hydroxide.
3.5. Analysis of the dialyzate for nitrite and nitrate.
National University of PharmacyDrug and Analytical Toxicology Department
LITERATUREMain
1. Karpushina S.A. Toxicological chemistry. Lecture course / S.A. Karpushina, V.S. Bondar, I.O.
Zhuravel. – Kharkiv: NUPh: Golden pages, 2011. – 208 p.
2. Toxicology: Summary of lectures, practice and tests on toxicology / S.M.Drogovoz, T.O.
Kutsenko, A.Yu. Pozdniakova, V.A. Ulanova. Kharkiv : NUPh : Golden Pages, 2011.– 88 p.
3. Karpushyna, S.A. Workbook for practical lesons on drug and analytical toxicology / S.A.
Karpushyna, S.V. Baiurka. – Kh.: NUPh Publishing, 2019. – 87 p.
4. Karpushina S.A. Toxicological chemistry. Schemes and Tables: Handbook for students of
higher schools / S.A. Karpushina, V.S. Bondar. – Kharkiv : NUPh : Golden Pages, 2009.– 120
p.
Auxiliary
1. Flanagan, R. J. Developing Analytical Toxicology Services: Principles and Guidance [Electronic
resource] / R. J. Flanagan. – Geneva : World Health Organization, 2005. – 36 p. – Available at :
http://www.who.int/ipcs/publications/training_poisons/hospital_analytical_toxicology.pdf (date of
the application : (07.09.2017). – Developing Analytical Toxicology Services: Principles and
Guidance.
2. Clarke's analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem
material: 4-th edition / A. C. Moffat; M.D. Osselton; B. Widdop [et al.]. – London, Chicago:
Pharmaceutical Press, 2011. – 2736 p.
3. Clarke’s Analytical Forensic Toxicology / Ed. by Sue Jickells, Adam Negrusz. – London:
Pharmaceutical Press, 2008. – 648 p.
National University of PharmacyDrug and Analytical Toxicology Department
Subject and applied aspects of
Analytical Toxicology
National University of PharmacyDrug and Analytical Toxicology Department
National University of PharmacyDrug and Analytical Toxicology Department
Analytical Toxicology definition
Analytical toxicology develops methods of chemicotoxicological
analysis of xenobiotics which are used for their determination in
various samples: namely,
the methods for sample preparation (isolation, purification,
concentration),
detection,
identification,
quantification of xenobiotics
and their metabolites in biological and other samples of the
toxicological study.
Assignments of Analytical Toxicology
Ad
ditio
nal
services
Analytical Toxicology
Analytical Forensic Toxicology (Forensic Chemistry)
(Task: to elucidate the questions that occur in
judicial proceedings)
Clinical Analytical Toxicology(Task: to assist in the treatment of the patients with cases
of acute or chronic poisonings)
Environmental Toxicology
Food Toxicology
Occupational Toxicology(Task: to study the agricultural products, water and air of
industrial ejections, domestic chemicals, etc. for the
presence of toxic substances to maintain the public health
legislation)
Analytical diagnostics of drug abuse
Analytical diagnostics of
acute intoxications
Analytical
diagnostics
abuse in sports
Therapeutic
Drug Monitoring
National University of PharmacyDrug and Analytical Toxicology Department
National University of PharmacyDrug and Analytical Toxicology Department
Analytical Forensic Toxicology
The task of Analytical Forensic Toxicology is determination of the cause of
lethal poisoning by a chemical substance during the forensic examination
Location: Medical Examiner’s Office.
Samples for research: evidence of poisoning, sectional material (stomach
with contents, liver, spleen, kidney, etc.), urine, blood, bile and other
samples.
National University of PharmacyDrug and Analytical Toxicology Department
Clinical Analytical Toxicology
Analytical diagnostics of acute intoxications
The task: to establish the nature of the poisonous substance and recommendations for
methods of detoxification (in cooperation with the physician).
Location: clinical laboratories of toxicological departments, laboratories of centers of clinical
toxicology, Office of Forensic Services.
Samples for research: blood, urine, saliva, sweat allocation, vomit masses, stomach
washings (first portions), liquid peritoneal dialysis and other samples.
Examination of alcohol, narcotic and toxic intoxication
The task: to determine the degree of alcohol intoxication and to establish the fact of the use
of narcotic and psychotropic substances for non-medical purposes.
Location: drug treatment centers
Samples for research: blood, urine, saliva, hair, nails, stomach ulcers and other samples.
National University of PharmacyDrug and Analytical Toxicology Department
Doping control
The task: to determine the use of doping agents
Location: laboratories accredited by the World Anti-Doping Agency (WADA)
Samples for research: biological fluids
National University of PharmacyDrug and Analytical Toxicology Department
Methodology of toxicological analysis
National University of PharmacyDrug and Analytical Toxicology Department
The general stages of any
forensic toxicological examination
No Stage
1 Detection – to detect any drugs or poisons in the samples submitted by
means of screening procedures
2 Identification – to identify conclusively any drugs, metabolites or poisons
present by means of specific relevant physicochemical tests
3 Quantification – to quantify accurately those drugs, metabolites or poisons
present
4 Interpretation – to interpret the analytical findings in (or and) in the context
of the case, the information given and the questions asked by the
investigating officer
National University of PharmacyDrug and Analytical Toxicology Department
The information for the analytical testing scheme design
No Data
1 Information from the accompanying documents (data from preliminary criminal
investigations or in subsequent court proceedings, conclusions of a medical examiner,
pathologist, etc.)
2 Results of external examination (colour, odour, consistance, presence or absence of
suspended solids or sediments, pH)
3 Results of preliminary tests (General Drug screening, preliminary tests for heavy metal
and arsenic compounds, alcohols, volatile poisons, organophosphorus pesticides, etc.)
National University of PharmacyDrug and Analytical Toxicology Department
Guiding principles of forensic
toxicology determined by its legal aspect
No Principle
1 All chemists who undertake this work must have toxicological experience
2 The analyst must be given a complete case history that contains all the
information available
3 All the evidential material, suitably labelled and sealed in clean containers,
must be submitted and examined
4 All the known identification tests should be applied and adequate notes
made at the time
5 All the necessary reagents used for these tests should be pure, and blank
tests should be performed to establish this fact
6 All tests should be repeated, and compared with control samples to which
the indicated poison has been added
National University of PharmacyDrug and Analytical Toxicology Department
Classification of poisons according to
their isolation method from biological material
Substances isolated by
mineralization of the sample
(Metal poisons)
Organophosphorus compounds, chlorinated pesticides,
derivatives of phenol and urine, carbonates, etc.
Substances isolated by extraction
with acidified water or acidified
ethanol (Drugs)
Hydrocyanic acid, acetic acid, halocarbons, alcohols,
aldehydes, phenols and cresols, aniline
Salicylates, barbiturates, pyrazolones, benzodiazepines,
phenothiazines, derivatives of p-aminobenzoic acid,
alkaloids
Barium, lead, manganese, chromium, silver, bismuth,
copper, cadmium, mercury, zinc, arsenic, antimony,
thallium compounds
Mineral acids, alkalies, ammonium, nitrate, nitrite
Fluoride, bromide, iodide
Substances isolated by steam
distillation (Volatile poisons)
Substances isolated by extraction
with organic solvents (Pesticides)
Substances isolated by extraction
with water
Substances isolated by special
methods
Substances detected in a
biological sample without
isolation
Carbon monoxide, hydrogen sulphide (in blood)
National University of PharmacyDrug and Analytical Toxicology Department
Physicochemical properties and usage of mineral acids,
alkalis, nitrite and nitrate
National University of PharmacyDrug and Analytical Toxicology Department
PHYSICOCHEMICAL PROPERTIES AND USAGE OF SOME
MINERAL ACIDS, ALKALIS, SALTS
Substance Physicochemical properties Usage
Sulphyric
acid
Transparent, colourless, oily liquid, well
soluble in water with the large exothermic
effect, hygroscopic, with specific pungent
odor and acidic taste
Manufacture of fertilization,
metallic alloys, chemical
reagents, dyes, leather, etc.
Nitric acid
Colourless or rather yellow liquid with
pungent choking odor and acidic taste,
well soluble in water with exothermic
effect, hygroscopic
Manufacture of fertilization,
explosive substances, dyes,
printing, etc.
Hydrochloric
acid
Colourless or rather yellow solution of
hydrochloride with water with acidic taste
and specific pungent odor
Medical practice,
hydrometallurgy,
galvanoplastics, can and textile
manufacturing
National University of PharmacyDrug and Analytical Toxicology Department
PHYSICOCHEMICAL PROPERTIES AND USAGE OF SOME
MINERAL ACIDS, ALKALIS, SALTS
Substance Physicochemical properties Usage
Sodium
hydroxide
White crystalline substance, well soluble
in water, ethanol
Manufacture of artificial textile,
soap, paper, petroleum industry
Potassium
hydroxide
White crystalline substance, well soluble
in water ethanol
Manufacture of soap, potassium
compounds and oxalic acid
Ammonium
hydroxide
Colourless solution of ammonia in water
with pungent odor
Chemical and refrigeration
industry, silvering.
Nitrite
Colourless or rather yellow crystalline
substance with salty taste, hygroscopic,
well soluble in water, moderate oxidizer,
destructing by acids with separation of
nitrogen oxides
Manufacture of dyes; in
medicine as vasodilators,
antidiarrheal and diuretic drugs,
antidote at cyanide poisoning
National University of PharmacyDrug and Analytical Toxicology Department
Toxicity of mineral acids, alkalis, nitrite
National University of PharmacyDrug and Analytical Toxicology Department
ROUTES OF ADMINISTRATION IN A BODY, LETHAL DOSES
AND MECHANISM OF TOXICITY OF SOME MINERAL ACIDS,
ALKALIES, SALTS
Substance Routes of
administration
Lethal dose Mechanism of toxicity
Sulphyric acid Mouth 5–10 g Proton causes an immediate
coagulation-type necrosis
that creates an eschar,
which tends to self-limit
further damage
Nitric acid Mouth, lungs 8–10 g
Hydrochloric
acid
Mouth, lungs 10–15 g
National University of PharmacyDrug and Analytical Toxicology Department
ROUTES OF ADMINISTRATION IN A BODY, LETHAL DOSES AND
MECHANISM OF TOXICITY OF SOME MINERAL ACIDS, ALKALIES,
SALTS
Sodium
hydroxide
Mouth, lungs (as
dust)
5–10 g Hydroxyl causes a liquefactive
necrosis with saponification and
continued penetration into deeper
tissues, resulting in extensive
damage
Potassium
hydroxide
Mouth, lungs (as
dust)
5–10 g
Ammonium
hydroxide
Mouth as solution,
lungs (as vapour)
10 ml of
25% solution
Sodium
nitrite
Mouth 1 g Nitrites are potent oxidizing
agents; oxidation of hemoglobin
may result in
methemoglobinemia, which
hinders oxygen-carrying capacity
and deliver
National University of PharmacyDrug and Analytical Toxicology Department
TOXICITY OF MINERAL ACIDS
Acid burn
National University of PharmacyDrug and Analytical Toxicology Department
TOXICITY OF ALKALIES
Alkali burn
National University of PharmacyDrug and Analytical Toxicology Department
The general scheme of chemical toxicological examination of
biological material for mineral acids, alkalis, nitrite and
nitrate
National University of PharmacyDrug and Analytical Toxicology Department
CHEMICAL TOXICOLOGICAL EXMINATION OF BIOLOGICAL MATERIAL FOR MINERAL
ACIDS, ALKALIES AND NITRITES
Samples: stomach with the contents,
vomit, food; additionally blood, urine
(nitrites, nitrates)
Preliminary examination: determinatin of sample pH ( acids, alkalies, ammonia)
Isolation: extraction by water (all mineral
poisons)
Purification of water extracts from
proteins by dialysis
Alkaline dialyzate (рН = 8– Acidic dialyzate (рН = 1–2)
Detection
Acids – by anion bound with proton
Alkalies – by sodium, potassium or
ammonium cations
Nitrite – by nitrite anion
Distillation of acids ( at the presence of
copper filings for sulpfuric and nitric acids)
Quantitative determination
Nitrite: photocolorimetry by
azodye formation
Acids and alkalies: potentiometry
National University of PharmacyDrug and Analytical Toxicology Department
DETECTION OF SOME MINERAL ACIDS, ALKALIES AND
NITRITES BY CHEMICAL REACTIONS
Substance Chemical reaction
Sulphuric acid Reaction with barium chloride
Reaction with lead acetate
Reaction with sodium rhodisonate and barium salt
Nitric acid Reaction with diphenylamine
Reaction with brucine in concentrated sulphuric acid.
Colouring wool yellow
Hydrochloric acid Reaction with silver nitrate
Reaction with potassium chlorate
Potassium hydroxide Reaction with sodium hydrotartrate
Reaction with sodium cobaltinitrite (Na3[Co(NO2)6])
Sodium hydroxide Reaction with potassium hydroxystibnate (K[Sb(OH)6])
Reaction with uranyl zinc acetate (Zn(UO2)3(CH3COO)8)
National University of PharmacyDrug and Analytical Toxicology Department
DETECTION OF SOME MINERAL ACIDS, ALKALIES AND
NITRITES BY CHEMICAL REACTIONS
Substance Chemical reaction
Ammonia (after
examination of a
biological sample for
hydrogen sulphide with
the reactive paper
moistened by lead acetate)
Reactions with litmus paper and reactive paper moistened by
copper sulphate
Reaction with Nessler’s reagent
Nitrite Reaction with sulphanilic acid and β-naphthol
Reaction with Griss reagent (sulphanilic acid and α-naphthyl
amine)
Reaction with iodine-starch paper
National University of PharmacyDrug and Analytical Toxicology Department
Analysis of the dialyzate for sulphuric, nitric and
hydrochloric acids
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR SULPHURIC
ACIDDistillation at the presence of copper filings
Collection of the distillate into iodine solution
2H2SO4 + Cu H2SO3 + CuSO4 + H2O;
H2SO3 SO2 + H2O;
SO2 + I2 + 2H2O H2SO4 + 2HI;
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR SULPHURIC ACID
Detection
Reaction with barium chloride → BaSO4 (white sediment)
Reaction with lead acetate → PbSO4 (white sediment)
PbSO4 + 4NaOH Na2PbO2 + Na2SO4 + 2H2O;
2PbSO4 + 2CH3COONH4
[Pb(CH3COO)2PbSO4] + (NH4)2SO4;
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR SULPHURIC ACID
Detection
Reaction with sodium rhodisonate and barium salt → (red
colour of barium rhodisonate disappears at addition of
sulphuric acid)
O
O
O
O
O
O
O
O
O
O
ONa
ONa
O
O
O
O
O
O
H2SO
4
O
O
O
O
ONa
ONa
BaSO4
+ 2+
Ba Ba + +
2Na ;
Ba + + .
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRIC ACID
Distillation at the presence of copper filings
2HNO3 + 3Cu 2NO + 3CuO + H2O;
3CuO + 6HNO3 3Cu(NO3)2 + 3H2O;
2NO + O2 2NO2;
2NO2 + H2O HNO2 + HNO3;
Assay of the distillate for the presence of nitrogenous acid and nitrite
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRIC ACID
Detection
Reaction with diphenylamine → blue colour
NH
NH NH
N N
H
NO3
-
H2SO4
NO3
-
2
+. HSO4
-
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRIC ACID
Detection
•Reaction with brucine in concentrated sulphuric acid → red colour
•Colouring wool yellow when heating → yellow colour turns orange when
treating the sample by ammonium
Removal of nitrogenous acid and nitrite
(urea, ammonium salts, sulphanilic acid are added)
O C(NH2)2
2HNO2 + 2N2 + CO2 + 3H2O;
HNO2 + NH4Cl N2 + 2H2O + HCl;
HNO2 + HOSO2NH2 N2 + H2SO4 + H2O;
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR HYDROCHLORIC ACID
•Reaction with silver nitrate → white sediment
HCl + AgNO3 AgCl + HNO3;
AgCl + 2NH4OH [Ag(NH3)2]Cl + 2H2O;
Assay of the distillate for the presence of sulphuric acid
Distillation from the dialysate
Detection
Reaction with potassium chlorate → colouring blue of iodine-starch paper
when iodine elaborating
KClO3 + 6HCl KCl + 3Cl2 + 3H2O;
Cl2 + 2Kl 2KCl + l2;
National University of PharmacyDrug and Analytical Toxicology Department
Analysis of the dialyzate for potassium hydroxide, sodium
hydroxide and ammonium hydroxide
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR POTASSIUM HYDROXIDE
Precondition – strong alkaline aqueous extracts from the sample by
phenolphthalein (pH 8–10)
Assay for the presence of carbonate (addition of BaCl2)
Neutralization of the dialyzate by СН3СООН solution (рН= 3–4)
Detection
Reaction with sodium hydrotartrate → КНС4Н4О6 (white sediment
soluble in hot water, mineral acids and alkali)
Reaction with sodium cobaltinitrite (III) (Na3[Co(NO2)6]) →
К2Na[Co(NO2)6] ((yellow sediment)
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR SODIUM HYDROXIDE
Precondition – strong alkaline aqueous extracts from the
sample by phenolphthalein (pH 8–10)
Neutralization of the dialyzate by СН3СООН solution
Detection
Reaction with potassium hydroxyl stibnate
K[Sb(OH)6] → КНС4Н4О6(white sediment soluble in hot water, mineral acids and alkali)
Reaction with uranyl zinc acetate
Zn(UO2)3(CH3COO)8 → NaZn(UO2)3(CH3COO)9(greenish-yellow crystalline sediment soluble in hot water and alkali)
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR AMMONIUM HYDROXIDE
Assay for the presence of hydrogen sulphide (test with lead
acetate )
Reaction with litmus paper (red colour turns blue) and
reactive paper moistened by copper sulphate →
[Cu(NH3)4]SO4 (blue colour)
Reaction with Nessler’s reagent → yellowish brown or
orange brown sediment
I Hg
I Hg
NH
NH4
++ 2 [HgI4]
2- + 2OH-
I + 5 I-+ 2 H2O.
National University of PharmacyDrug and Analytical Toxicology Department
Analysis of the dialyzate for nitrite and nitrate
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRITE
Reaction with sulphanilic acid and β-naphthol → orange-
red colour
HNO2 + NH
2HO
3S NHO
3S N
NHO3S N
OH
N NNaO3S
+ HCl+
Cl-
+ 2 H2O ;
+Cl
-+ + 2 NaOH
+ NaCl + 2 H2O
NaO
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRITE
Reaction with Griss reagent (sulphanilic acid and α-naphthyl
amine in acetic acid) → orange-red colour
NH2
HO3S NHO
3S N
NHO3S N
NH2
N NHO3S NH
2
HNO2 + + CH3COOH+
CH3COO-
+ H2O ;
+CH3COO
-+
+ CH3COOH .
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRITE
Reaction with 1,8-naphthalene diamine → 1,8-azimino
naphthalene (orange-red colour solution or sediment)
NH2
NH2 N
N
N
H
HNO2 + + 2 H2O .
Reaction with iodine-starch paper → blue sport
National University of PharmacyDrug and Analytical Toxicology Department
ANALYSIS OF THE DIALYSATE FOR NITRATE
Assay for the presence of nitrite
(Nitrite can be decomposed by addition of sulphamic acid,
sodium azide or urea)
Reaction with diphenylamine → blue colour
Reaction with brucine in concentrated sulphuric acid →
red colour
Reaction with iron (III) sulphate and concentrated
sulphuric acid → brown ring around iron (III) sulphate
crystal
National University of PharmacyDrug and Analytical Toxicology Department
National University of PharmacyDrug and Analytical Toxicology Department
1. Therapeutic Drug Monitoring.
2. Environmental Toxicology.
3. Food Toxicology.
4. Occupational Toxicology.
5. Usage of mineral acids, alkalis, nitrites and nitrates in the national
economy and medicine.
6. Toxicity and treatment of nitrate and nitrite poisonings. Antidote
therapy.
7. Physical basis of the dialysis method.
8. Quantitation methods of mineral acids, alkalis and nitrites in dyalisate.
Students' Individual Work Tasks
National University of PharmacyDrug and Analytical Toxicology Department
This topic forms the basis of expert thinking, promotes the development of skills in the
field of Forensic and Clinical Toxicology (the Medical Examiner’s Offices, the
Emergency Centre for acutely poisoned patients, the Industrial Sanitary Laboratory
which performs industrial and ecological supervision, the Toxicological Laboratory for
Diagnostics of drug abuse and alcoholism).
The knowledge of toxicokinetics of mineral acids, alkalis, nitrites and
nitrates is necessary to a pharmacist to prevent intoxications by this group
of substances that are used as medications and in the production of
medicines.
This topic gives the methodical basis to the toxicologist to correctly construct
an algorithm for carrying out the toxicological research and interpreting its
results for this group of toxicants.
Сonclusions
Thank you for your attention
National University of PharmacyDrug and Analytical Toxicology Department
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