CARBETAMIDE 95

CARBETAMIDE
95

O
H
N O C
CH NHC2H5
C
O CH3

ISO common name Carbetamide

Chemical name (R)-1-(Ethylcarbamoyl)ethyl phenylcarbamate
(IUPAC); (R)-N-ethyl-2-[[(phenylamino)carbo nyl]-
oxy]propanamide (CA; 16118-49-3)
Empirical formula C12H16N2O3
RMM 236.3
m.p. 119 °C
v.p. 3 × 10-7 Pa at 20 °C
Solubility In water: 3.5 g/l at 20 °C; readily soluble in
acetone, dichloromethane, dimethylformamide,
ethanol and methanol, barely soluble in cyclo-
hexanone and petroleum ether
Description Colourless, odourless crystals
Stability Stable under normal storage conditions
Formulations Emulsifiable concentrates and wettable powders

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 CARBETAMIDE 95

CARBETAMIDE TECHNICAL
*
95/TC/M/-

1 Sampling. Take at least 100 g.

2 Identity tests.
2.1 HPLC. Use the HPLC method below. The relative retention time of
carbetamide with respect to the internal standard for the sample solution should
not deviate by more than 2% from that for the calibration solution.
2.2 Infrared. Prepare potassium bromide discs from the sample and from pure
carbetamide using 1.3 to 1.5 mg material and 300 mg potassium bromide. Scan
the discs from 4000 to 400 cm-1. The spectrum produced from the sample disc
should not differ significantly from that from the standard.
2.3 Optical rotation. The optical rotation power determined by the method
below should not be outside of the range 19-23 °.

REAGENTS
N,N-dimethylformamide

APPARATUS
Polarimeter fitted with a sodium vapour lamp and a 20 cm length polarimeter
tube. A constant temperature of 20 °C is maintained in the tube by means of
circulating water.

PROCEDURE
Weigh (to the nearest 0.1 mg) into a volumetric flask (50 ml) 4.9 to 5.1 g of
sample. Dissolve in and dilute to the mark with N,N-dimethylformamide. Fill the
tube with this solution and place the filled tube in the polarimeter. Allow to
reach thermal equilibrium and measure the magnitude of the optical rotation.

Specific rotation for the solution at the sodium D-line:

A
[a]20
D 25
E

where:
E = mass of the sample dissolved in 50 ml of solution (g)
A = angular rotation (degrees)

*
CIPAC method 1991. Prepared by the French Committee; Chairman: B Declercq. Based on a method supplied
by Rhône Poulenc Agro, France

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 CARBETAMIDE 95

3 Carbetamide
OUTLINE OF METHOD Carbetamide is determined by high performance liquid
chromatography using the internal standardization method.

REAGENTS
Acetonitrile HPLC grade
Methanol HPLC grade
Water HPLC grade
Mobile phase. Add 50 ml methanol to 400 ml acetonitrile and fill up to 1000 ml
with water.
Carbetamide standard of known purity
Diethyl phthalate internal standard
Internal standard solution. Weigh into a volumetric flask (100 ml) about 50 g
diethyl phthalate. Dissolve in and dilute to the mark with acetonitrile.
Calibration solution. Weigh (to the nearest 0.1 mg) into an Erlenmeyer flask
enough sample to contain 0.09 to 0.11 g carbetamide standard (s g). Add by
pipette internal standard solution (5.0 ml) and about 45 ml acetonitrile.
Dissolve by sonication for 2 min, or by mechanical shaking for 30 min (stock
solution). Transfer by pipette 10.0 ml of this solution to an Erlenmeyer flask
(250 ml). Add about 90 ml acetonitrile and homogenize.

APPARATUS
Liquid chromatograph equipped with a constant flow pump, an UV detector
capable of measuring at 235 nm, a column oven, a loop injector and an electronic
integrator
Column stainless steel, 250 × 4 (i.d.) mm packed with Lichrosorb RP18 5 µm
Filtration device consisting of a glass syringe fitted with a membrane filter
unit (Millex-SR 0.5 µm, Millipore art. SLSR 025 NB; Minisart SRP 15, 0.2
µm, Sartorius art. no 17558 K or equivalent).
Ultrasonic bath or mechanical shaker

PROCEDURE
(a) Chomatographic conditions (typical):
Eluant flow rate 1 ml/min
Column temperature 40 °C
Injection volume 10 µl
Detector wavelength setting 235 nm
Running time 15 min
Retention times carbetamide : 4.9 min
diethyl phthalate : 10.1 min

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 CARBETAMIDE 95

(b) Preparation of sample solution. Weigh (to the nearest 0.1 mg) into an
Erlenmeyer flask (250 ml) enough sample (w g) to contain 0.09 to 0.11 g
carbetamide. Add by pipette internal standard solution (5.0 ml) and about 45 ml
acetonitrile. Dissolve by sonication for 2 min, or by mechanical shaking for 20 min.
Transfer by pipette 10.0 ml of this solution to an Erlenmeyer flask (250 ml). Add
about 90 ml acetonitrile and homogenize.
(c) Determination. Inject 10 µl portions of the calibration solution until the
response ratio of the carbetamide peak relative to the internal standard peak
agrees within 1% for successive injections. Then inject in duplicate 10 µl
portions of the sample solution followed by another calibration solution
injection. Measure the peak areas of the relevant peaks. Calculate the response
factors (f) from the calibration solution injections preceding and following the
injections of the sample solution. Average the values obtained.
(d) Calculation
Ir s P
f
Hs

Hw f
Content of carbetamide g/kg
Iq w

where:
Hs = area of the carbetamide peak in the calibration solution
Ir = area of the internal standard peak in the calibration solution
Hw = area of the carbetamide peak in the sample solution
Iq = area of the internal standard peak in the sample solution
s = mass of carbetamide in the calibration solution (g)
w = mass of sample taken (g)
P = purity of carbetamide standard (g/kg)

Repeatability r = 19.0 to 21.3 g/kg at 957 g/kg active ingredient content

Reproducibility R = 26.7 to 27.9 g/kg at 957 g/kg active ingredient content

31
 CARBETAMIDE 95

CARBETAMIDE EMULSIFIABLE CONCENTRATES

*
95/EC/(M)/-

1 Sampling. Take at least 500 ml.

2 Identity tests
2.1 HPLC. As for carbetamide technical 95/TC/M/2.1.

3 Carbetamide. As for carbetamide technical 95/TC/M/3.

NOTE The emulsifiable concentrate contains an ingredient with a retention

time of about 6.3 min. Before performing the determination make sure that the
separation of the peaks of carbetamide and this ingredient is acceptable.

Repeatability r = 5.0 to 6.5 g/kg at 287 g/kg active ingredient content

Reproducibility R = 5.4 to 7.2 g/kg at 287 g/kg active ingredient content

CARBETAMIDE WETTABLE POWDERS

*
95/WP/M/-

1 Sampling. Take at least 500 g.

2 Identity tests
2.1 HPLC. As for carbetamide technical 95/TC/M/2.1.

3 Carbetamide. As for carbetamide technical 95/TC/M/3, except:

(b) Preparation of sample solution. Weigh (to the nearest 0.1 mg) enough
sample (w mg) to contain 0.09 to 0.11 g carbetamide. Add by pipette internal
standard solution (5.0 ml) and about 45 ml acetonitrile. Extract by sonication for
2 min, or by mechanical shaking for 30 min. Transfer by pipette 10.0 ml of this
solution to an Erlenmeyer flask (250 ml). Add about 90 ml acetonitrile and
homogenize. Withdraw a few mls of the supernatant solution and filter through
the membrane filter unit. Use the filtered solution for the determination.

Repeatability r = 15.3 to 24.0 g/kg at 700 g/kg active ingredient content

Reproducibility R = 17.6 to 28.8 g/kg at 700 g/kg active ingredient content

*
CIPAC method 1991. Prepared by the French Committee; Chairman: B Declercq. Based on a method supplied
by Rhône Poulenc Agro, France

32
 CARBETAMIDE 95

4 Suspensibility

REAGENTS and APPARATUS

As for MT 15, CIPAC F, p. 45 and for method 95/TC/M/2 except:
Internal standard solution. Weigh into a volumetric flask (100 ml) about 2.5 g
of diethyl phthalate. Dissolve in and dilute to the mark with acetonitrile.
Calibration solution. Weigh (to the nearest 0.1 mg) into an Erlenmeyer flask
(250 ml) about 0.25 g of carbetamide standard (s g). Add by pipette internal
standard solution (25.0 ml) and about 100 ml acetonitrile. Dissolve by
sonication for 2 minutes or by mechanical shaking for 30 minutes (stock
solution). Transfer by pipette 10.0 ml of this solution to an Erlenmeyer flask
(250 ml). Add about 90 ml acetonitrile and homogenize.

PROCEDURE
(a) Preparation of suspension MT 15.1 (i)
(b) Determination of suspensibility MT 15.1 (ii)
(c) Preparation of the bottom 25 ml of suspension for analysis. After removal
of the top 225 ml of suspension, add by pipette internal standard solution
(25.0 ml) and about 100 ml of acetonitrile. Shake well and place in an ultrasonic
bath for 2 minutes. Transfer by pipette 10.0 ml of this solution to an Erlenmeyer
flask (150 ml). Add about 90 ml acetonitrile and homogenize. Withdraw a few
mls of the supernatant solution and filter through the membrane filter unit.
(d) Determination of carbetamide in the suspension. Using the conditions
described in 95/TC/M)/3 (a), inject 10 µl portions for the calibration solution
until the response factor for successive injections agree within 2%. Then inject
10 µl portions of the sample solution. Measure the peak areas of the relevant
peaks.
(e) Calculation. Calculate the response factor (f) from the calibration solution
injections preceding and following the injections of the sample solution.
Average the values. The response factor is:

Ir s P
f
Hs
where:
Hs = area of the carbetamide peak in the calibration solution
Ir = area of the internal standard peak in the calibration solution
s = mass of carbetamide in the calibration solution (g)
P = purity of carbetamide standard (g/kg)

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 CARBETAMIDE 95

Hw f
Mass of carbetamide g/kg
Iq w
where:
Hw = area of the carbetamide peak in the sample solution
Iq = area of the internal standard peak in the sample solution
f = average response factor

111 ( c - Q )
Suspensibility =
c

where:
c = mass of carbetamide on the sample taken for the preparation of the
suspension (g)
Q = mass of carbetamide in the 25 ml remaining in suspensibility cylinder

34