Quality Control of Cytotoxic Drugs

8/3/2019 Quality Control of Cytotoxic Drugs

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QUALITY CONTROL TESTS OFCYTOTOXIC DRUGS

(CYTARABINE)

FRESENIUS KABI ONCOLOGY(DABUR PHARMA LTD.)

SOLAN,HIMACHAL PRADESH

PRESENTED BY:

PREETIKA RATHOUR

ROLL NO. 301001018


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QUALITY CONTROL OFCYTOTOXIC DRUGS

Quality can be defined as status of drug that is

determined by identity, purity, content and otherchemical, physical or biological properties of the drug.

Quality control refers to processes involved inmaintaining the quality and validity of manufacturedproduct.


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It is the process or system for monitoring the

quality of laboratory testing, and the accuracyand precision of results.

Data is routinely collected and analyzed fromevery test run or procedure.It allows forimmediate corrective action.

It is responsible for the acceptance and rejectionof the incoming raw materials,packagingcomponents,in process tests and finally forapproved or rejection of finished products.


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Microbiology QC: To check sterility,Ability tosupport growth,Selective or inhibitorycharacteristics of the medium and to test QC

organisms with each new batch or lot number tocheck for growth of fastidious organisms onmedia of choice and incubate at time andtemperature recommended


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CYTOTOXIC DRUGS:

Cytotoxic drugs (CDs) are used as anti- cancerdrugs.They kill cancer cells or stop them frommultiplying in different ways. However, they all tendto work by interfering with some aspect of celldivision and multiplication.

Cytotoxic drugs are effective where cells are rapidly

dividing.However, some normal cells in the bodydivide and multiply quite rapidly like hair cells, bonemarrow cells, and cells lining the mouth andgut,these may be affected by cytotoxic drugs.


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Ara-C (ArabinofuranosylCytidine) injection

Cytarabine, or Cytosinearabinoside, is a chemotherapyagent used mainly in the treatment of

cancers of white blood cells such asacute myeloid leukemia or nonHodgkin lymphoma.

The empirical formula isC9H13N3O5 and has a molecular

weight of 243.217 g/mol.

Cytarabine is an odourless,white tooff-white, crystalline powder is freelysoluble in water and slightly soluble

in alcohol and in chloroform.
http://en.wikipedia.org/wiki/Carbonhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Oxygenhttp://en.wikipedia.org/wiki/Nitrogenhttp://en.wikipedia.org/wiki/Hydrogenhttp://en.wikipedia.org/wiki/Carbon


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PHARMACODYNAMICS

Cytarabin destroys cancer cells

by interfering with DNAsynthesis.

Cytosine normally combines withdeoxyribose, to formdeoxycytidine.

Cytosine arabinoside is similarenough to cytosine deoxyribose(deoxycytidine) to beincorporated into human DNA,

but different enough that it killsthe cell.

It inhibits both DNA and RNApolymerases and nucleotidereductase enymes needed for

DNA sythesis.


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DIFFERENT

INSTRUMENTS USED TOCHECK QUALITY


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1. pH METER:

It is used to determine the acidity or alkalinity of thesolution.

According to the defined standards or the technicalinformation of Cytarabine,pH should be from 7 to 9.

The test performed for pH of cytarabine with

concentration of 20mg/ml,its pH range was found outto be 7.2-8.0.


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2. AUTO KARL-FISCHER TITRIMETER:

Karl fischer apparatus is used for

determination of the moisture of thedrug or determination of water.

The anodic compartment containsthe anolyte solution which includes

sulfur dioxide (SO2), iodide (I-

) andimidazole needed in the chemicalreaction. Methanol or ethanol (ROH)is usually used as a solvent.

ROH+SO2+RN (RNH).SO3R

RNH.SO3R+2RN+I2+H2O(RNH).SO4R+2(RNH)I

2I- I2+2e-


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Water (%W/V) =V*F*100/W

Where,V=volume of the reagent consumed (in ml)

F= water equivalence factor of the reagent

(mg/ml)W= weight of sample taken in mg

Determination of water using KF (Karl Fischer)

coulometric titration for determining free waterand water of hydration in most solid or liquidorganic and inorganic compounds was found tobe .05% -1%. The KF of samples found to be0.50% ,within the specified limits.


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3. FOURIER TRANSFORMINFRA REDSECTROPHOTOMETER

FTIR is most useful for identifying chemicals andis most powerful tool for identifying types ofchemical bonds (functional groups).

The wavelength of light absorbed ischaracteristic of the chemical bond. By

interpreting the infrared absorption spectrum,the chemical bonds in a molecule can bedetermined.


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Wavenumber (cm-1)


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4. UV SPECTROPHOTOMETER

UV Spectrophotometers can be divided into 2ranges:-Far UV or under vacuum: 185-200nm

-Near UV without vacuum: 200-400nm

When radiation is passed through a layer of thesolution containing an absorbing substance, partof the radiation is absorbed, the solution is lessthan the intensity of the radiation. Themagnitude of the absorption is expressed as:

A=log10 (I0/I)


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For the selection ofanalytical wavelength,15g/mL solution wasprepared by subsequentdilutions and was

scanned in the spectrummode from 200nm-400nm.

The peak height ofCytarabine was at itsmaximum at 280 nm.


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5.High Performance Liquid Chromatography

Separation of components from one another bythe column packing that involves variouschemical and/or physical interactions betweentheir molecules and the packing particle.

These separated components are detected atthe exit of the column by a detector thatmeasures the amount. An output from this

detector is called a liquid chromatogram.

Here separation is more effective due to greatersurface area achieved due to very small particle

size of stationary phase.


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HPLC GRAPH OF STANDARD

The Retention time was found to be 11.43 minutes.


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The Retention time was found to be 11.45 minutes.

HPLC GRAPH OF UNKNOWN


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The representative chromatogram of standardsolution alone and that containing 15ml of Cytarabine

showed almost same retention time.

Thus, absence of any overlapping or extraneous peaks

in both chromatograms indicates its specificity.

Area Purity

Standard 9180640 100%

Sample 8670644 94.44%

Thus, as the % purity was almost close to the

standard, we could say that our sample of Cytarabine

was pure.


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6.Test for Visible and Sub visibleparticles:

TEST RESULT SPECIFICATION

Visibleparticles

Solution isfree fromvisible

particles

Practicallyfree fromvisible

particles.Sub-visibleparticles

>=10m 17partilcesper vial

Not morethan 6000per vial.

>+25m 1 particlesper vial

not morethan 600 pervial.

Various suspendedparticles are observed

under the beam oflight and if too manysubvisible particlesbetween size 10 m

to 25 m then batch isrejected.


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6.MICROBIOLOGICAL QC

When performed a microbiological assay for anystrains present in the vial, no turbidity was

observed .

Samples from vials are serial diluted and then

plated on different media and no growth wasobserved.


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CONCLUSION

Thus the above tests performed helps in

survey of the market value of the drug andpharmaceutical company and stability,which

explains its national as well as international

market, in terms of its therapeutic effects


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Quality Control of Cytotoxic Drugs