Analytical aspect of chlorpromazine

1. Batch : 2019-2020 1

2. INDEX
Sr no Points of psychose
1 Introduction
2 Classifications
3 Phenothiazine-typical
4 Introduction to chlorpromazine
6 Pharmacokinetic
7 Synthesis
8 Mechanism of action
9 Case study
10 Conclusion and result
11 Reference
Batch : 2019-2020 2

3. ANTIPSYCHOTIC
• Antipsychotics, also known as neuroleptic or major tranquilisers, are class of
medication primarily used to manage psychosis principally in schizophrenia
or bipolar disorder.
• Antipsychotics are those, used in relieving the symptoms of schizophrenia.
• The cause of schizophrenia remains unclear but it involves a combination of
genetic and environmental factors.
• As far as biochemical aspect it concerned strong evidence supporting
dopamine overactivity hypothesis.
• Many of drugs useful in psychosis are dopamine antagonists.
• There is increased concentration of dopamine in amygdala in schizophrenic
patient
Batch : 2019-2020 3

4. CLASSIFICATION
Classification of antipsychotics :
A)TYPICAL ANTIPSYCHOTICS :
1)Phenothiazine e.g. chlorpromazine,acetophenazine
2)Rauwolfia alkaloids e.g.reserpine
3)Thioxanthenes e.g.chlorprothixene
4)Butyrophenones e.g. halo peridot
5)Dibenzoxazepine e.g.loxapine
B)ATYPICAL ANTIPSYCHOTICS:
1)Dibenzoxazepine schizophrenia e.g.clozapine,olanzapine
2)Benzamide e.g.sulpiride
3)Diphenylbutylpiperidines e.g.pimozide,risperidone
4) Others e.g. Sertindol
Batch : 2019-2020 4

5. Batch : 2019-2020 5

6. PHENOTHIAZINE
Chemistry :
Phenothiazine have three ring structure in which two benzene rings are
joined by 'S' and 'N',substitution are there at position 2 or 10.
Transqullizing property is there if there is 3 carbon bridge between the 'N'
atom of the ring and side chain atom position 10.For e.g.,chlorpromazine
posses activity and promethazine does not have any antipsychotics activity.
Batch : 2019-2020 6

7. On the basis of sterechemical model and crystallographic data
structures of phenothiazine have similarity with dopamine and
noradrenaline.
Phenothiazines possess alpha blocking and dopamine receptor
blocking activity.
Nature of substitution at position 10 influence pharmacological
activity.
Substitution can be aliphatic (chlorpromazine
),piperidine(thioridazine) or piperazine (trifluperazine).
Piperidine substitution results in compound having lower
incidences of extrapyramidal side effects.
Piperazine posses most potent antipsychotics activity but at
same time produce extrapyramidal side effects.
Substitution of 2 may be 'Cl',SCH3 or CF3.
Batch : 2019-2020 7

8. CHLORPROMAZINE
This is also referred to as 'Largactil' because of it's "large acting "properties
having number oof varied effects.
Pharmacological action:
CNS: chlorpromazine produces psychomotor slowing in patients with
psychosis .there is emotional quietening and diminished anxiety without any
impairment or a wakefulness.
It blocks the conditioned avoidance response in animals.
It potentiate the analgesic activity of morphine.
It depresses the release of a number of hormones such as growth hormone
,prolactin,antidueritic hormone (ADH) etc.
Batch : 2019-2020 8

9. Batch : 2019-2020 9
Synthesis:

10. Mechanism of action:
It is well absorbed orally from the g.i.tract .After absorption ,it
is distributed in the body tissues,achieving higher
concentrations in lungs ,liver and adrenals.Metabolism occurs
in liver and the metabolites are excreted through urine.
Therapeutic Uses:
1. Schizophrenia and major psychosis.
2. Aggressive or destructive behaviour in children.
3. As antiemetic and anti-cough agent.
4. As pre anaesthetic agent.
Adverse effect :
chlorpromazine can produce obstructive jaundice but
thioridazine,halo peridol, and atypical antipsychotics don't
produce jaundice.clonazapine can produce agranulocytosis, also
produce weight gain.sertindol may also produce ventricular
dyrrthmias.
Batch : 2019-2020 10

11. CASE STUDY
Chloropromazine contain not less than 98.0 percent and not more than 101.5 percent of
C17H19ClN2S. HCl
The IUPAC name of chlorpromazine hydrochloride is 3-(2-chlorophenothiazine-10-yl) propyl
dimethyl-amine.
Identification:
1) By infrared absorption (197K)
2) The principle spot found in the Test for Other alkylated Phenothiazine corresponded in Rf to
spot From the standard pharmaceutical solution.
3) A Solution responds to test For chloride.
4) Melting range:between 195 to 198
5) UV spectroscopy
Batch : 2019-2020 11

12. IR spectrophotometer:
Batch : 2019-2020 12
IR radiation are used for identification of chlorpromazine solution
By means of instrumentation of IR spectrophotometer.

13. IR of CHLORPROMAZINE:
Batch : 2019-2020 13

14. MATERIALS
Batch : 2019-2020 14
All chemical used were of analytical grade. Cpn HCL waspurchased from Sigma (Fw: 355.3), neurazine
tablets (100 mg/tablet) and bromophenol blue indicator.
Diluent preperation:
Distilled water is used as diluent.
Standard preparation:
Bromophenol blue (1×10-3 M) and Cpn HCL(1×10-3) stocksolution was prepared to be used for the preparation
of standard solutions.In 100 ml volumetric flask,15 ml BrPB,3 ml citrate buffer (pH 3) & different aliquots of
Cpn HCL were added to prepare 5 standard solutions of Cpn HCL range in concentration from 2.553-
16ppm.the five standard solutions were scanned for maximum wavelengths,and calibration was done to
perform linearity test.
Pharmaceutical preparation:
Ten tablets of neurazine formulation were ground and weighed (4.4870). Each tablet contained 100
mg active ingredient of Cpn HCL to prepare stock solution(1×10-3) of the formulation,0. 1594 g of
the ground tablet were weighed & dissolve with distilled water in a 100 ml volumetric flask.The
stock solution was diluted to prepare(1×10-4).a test solution was made by adding 15 ml
bromophenol blue,citrate buffer,and10 ml neurazine(1×10-4).The solution was tested by the
extrapolation method to determine the concentration of neurazine test sample.
Instrumentation:
UV-visible double beam spectrophotometer with matched quartz cell(1cm)

15. RESULTS
Batch : 2019-2020 15
• Development and optimization of spectrophotometric
Method:
The selection of proper wavelength in this method depends
on the sample,diluent and test solutions.
• Selection of wavelength:
The standard wavelength for pharmaceutical solution
ranges from 200 to 700 nm.
• Method of validation:
1. specificity
2. Linearity
3. Precision
4. Accuracy
5. Robustance
6. System suitability

16. Batch : 2019-2020 16
• Conc vs absorbance study on linearity:
LINEARITY
Conc (ppm) Absorbance
0 0.0000
2.5 0.180
3.55 0.223
5.33 0.417
7.106 0.489
8.825 0.615
10.659 0.691

17. CONCLUSIONS
The results obtained clearly demonstrate the
suitability of using bromate-bromide mixture and two
dyes for the micro determination of chloropromazine.
The versatility and simplicity of the titrimetric
technique employing bromate-bromide mixture is
clear from a large number of pharmaceutical
substances that were assayed.
Batch : 2019-2020 17

18. REFERENCE
Batch : 2019-2020 18
1. Karpinska J, Starczewska B, Puzanowska-Tarasiewicz H (1996) Analytical
properties of 2- and 10-disubstituted phenothiazine derivatives. Anal Sci 12:
161-167.
2. Minakata K, Suzuki O, Ishikawa Y, Seno H, Harada N (1992) Determination
of
molar absorptivities of radicals of 18 phenothiazine derivatives. Forensic Sci
Int 52: 199-210.
3. Shi W, Yang J, Haung Y (2004) Ion-pair complex-based solvent extraction
combined with chemiluminescence determination of chlorpromazine
hydrochloride with luminal in reverse micelles. Journal of Pharmaceutical and
Biomedical Analysis 36: 197-203.

19. THANK YOU
Batch : 2019-2020 19