Page 15 - Shimadzu’s Solutions for Impurities Analysis

FDA Regulations on
Residual Solvents
Headspace GC
Data

Analysis Using the GC-2010 Plus with a Headspace Sampler
The U.S. Pharmacopoeia, European Pharmacopoeia and "Guidelines for Residual Solvents in Drug Products" notified by
the former Japanese Ministry of Welfare classify solvents according to toxicity as Class 1 (Solvents to be avoided), Class 2
(Solvents to be limited), and Class 3 (Solvents with low toxic potential). The analysis of Class 1 solvents (aqueous
solution) and Class 2 solvents (aqueous solution) are introduced below. Genotoxic Impurities FDA Regulations on

+*,` 11DDEy : 1,1-Dichloroethene
111TCEa : 1,1,1-Trichloroethane
CCl4 : Carbon Tetrachloride
;*,H Bz : Benzene
12DDEa : 1,2-Dichloroethane
)a
+*,H
**S

0.0 2.5 5.0 7.5 10.0 12.5 min
Fig. 1 Class 1 Solvent Standard Sample (Aqueous Solution, Procedure A)

+*4 J`J* 4LJ`J* ;VS *0)a ,[)a MeOH : Methanol Residual Solvents FDA Regulations on
[YHUZ +*,` JPZ +*,` ;/- T¶? W¶? V¶? DCM : Methylene Chloride
AcNt : Acetonitrile
trans12DCEy : Trans-1,2-Dicthenehloroethene
4L6/ cis12DCEy : Cis-1,2-Dichloroethene
THF : Tetrahydrofuran
cycC6 : Cyclohexane
MecycC6 : Methylcyclohexane
(J5[ 1,4-D : 1,4-Dioxane
¶+ ClBz : Chlorobenzene
Tol : Toluene
EtBz : Ethylbenzene
m-X : m-Xylene
5.0 10.0 15.0 20.0 25.0 30.0 min p-X : p-Xylene
o-X : o-Xylene
Fig. 2 Class 2 Solvent Standard Sample (Aqueous Solution, Procedure A)

* ;L[YSU C6 : Hexane Inorganic Impurities FDA Regulations on
NtMe : Nitromethane
;*,` 4)2 CRF : Chloroform
12DMOEa : 1,2-Dimethoxyethane
TCEy : Trichloroethylene
Pyr : Pyridine
MBK : Methylbutylketone
*9- Tetrln : Tetralin
5[4L +46,H 7`Y

5.0 10.0 15.0 20.0 25.0 30.0 min
Fig. 3 Class 2 Solvent Standard Sample (Aqueous Solution, Procedure B)

GC Analytical Conditions Headspace Analytical Conditions
Column : Rtx-624 30m×0.53mmI.D. 3 μm Equilibration Temp. : 80ºC
Carrier Gas : He 35cm/sec, Split ratio 1:10 Equilibration Time : 60 min
Detector : FID Support from Shimadzu
Inj.Temp. : 140ºC
Det. Temp. : 250ºC
Col. Temp. : 40ºC(20 min) – (10ºC/min) – 240ºC(20 min)

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