determination of manufacturing and degradation and residual solvent by gas chromatography

1. DETERMINATION OF MANUFACTURING AND
DEGRADATION RESIDUE AND RESIDUAL SOLVENTS
BY GAS CHROMATOGRAPHY
PRESENTED BY: ANAY PRATAP SINGH
M.PHARM,1st SEM(PHARMACEUTICS)
DEPARTMENT OF PHARMACY
B.U.

2. GAS CHROMATOGRAPHY
INTRODUCTION:
• Separation of gaseous or volatile substances.
• Simple and efficient in regarded to separation. Gas
consist of Gas Solid Chromatography(GSC), Gas
Liquid Chromatography(GLC).
• Gas- mobile phase
• solid/liquid- stationary phase
• GSC is not used because of limited number of
stationary phase.

3. PRINCIPLE
• GSC principle is ADSORPTION
• GLC principle is PARTITION
• Sample to be separated is converted to vapour and mixed with
gaseous mobile phase.
• Component more soluble in the stationary phase – travels
slower
• Component less soluble in the stationary phase -- travels
faster

4. INSTRUMENTATION

5. Determination of Manufacturing and
Degradation Residues by GC
1.DETERMINATION OF PIVALIC ACID IN DIPIVEFRIN
EYE DROPS
GC provide a useful technique for estimating
volatile degradation product. For example, the
pivalic acid release from the hydrolysis of
dipivefrin in eye drops preparation used for
treating glaucoma may be estimated by GC.

6. Isovaleric acid,which is an isomer of pivalic
acid provides a suitable internal standard.
Breakdown products of ester are more likely
to occur in aqueous formulation such as
eyedrops or injection

7. 2.DETERMINATION OF DIMETHYLANILINE
IN BUPIVACAINE INJECTION
Dimethylaniline is both a manufacturing
impurity in bupivacaine and since it is
formulated in injection, a possible breakdown
product, although hydrolysis of amides is
much slower than hydrolysis of ester.

9. 3.DETERMINATION OF N,N-
DIMETHYLANILINE IN PENICILLINS
Determination of N,N-Dimethylaniline in
penicillins is carried out by GC. In this case the
dimethylaniline is present in the sample since
it is used as a counter ion in the purification of
the penicillins by recrystallisation . The aniline
counterion can be easily removed by mild
basification and extraction.

10. 4.DETERMINATION OF RESIDUAL
GLUTARALDEHYDE IN A POLYMERIC FILM
Sometimes derivatizations can provide a highly
specific method of detecting impurities. In this
example,the low molecular weight impurity
glutaraldehyde which is not stable to direct
analysis by GC, is reacted with a high molecular
weight derivatization reagent
pentaflurobenzyloxime;the reaction is shown.

12. Determination of Residual Solvent
1.DETERMINATION OF RESIDUAL SOLVENTS AND
VOLATILE IMPURITIES BY HEADSPACE
ANALYSIS
The simplest method of sampling is to put the
sample into a sealed vial and heat is as shown.

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