BENSULTAP 464
BENSULTAP
464
O
H3C S S
O
N
O
H3C S S
O
ISO common name Bensultap
Chemical name S,S'-2,2-Dimethylamino trimethylene di(benzenethio-
sulfonate) (IUPAC and CA ; 17606-31-4)
Empirical formula C17H21NO4S4
RMM 431.63
m.p. 83-84 °C
Solubility In water: 0.7 to 0.8 mg/l at 30 °C; in methanol: 25 g/l;
ethanol: 13 g/l; n-hexane: 0.17 g/l; xylene: 77 g/l;
acetonitrile: more than 1000 g/l; N,N-dimethyl-
formamide: more than 1000 g/l. all at 25 °C
Description The pure material is a white crystalline solid. The
technical material is a pale yellow crystalline powder
with a slight characteristic odour.
Stability Stable in acidic conditions but hydrolysed in neutral of
alkaline conditions
Formulations Wettable powders, emulsifiable concentrates,
suspension concentrates and dustable powders
BENSULTAP TECHNICAL
*
464/TC/M/-
1 Sampling. Take the least 100 g.
2 Identity tests
2.1 HPLC. Use the HPLC method below. The retention time of bensultap
should not deviate by more than 2% from that of calibration solution.
*
CIPAC method 1991. Prepared by the Japanese Committee (JAPAC). Chairman: Dr. T Suzuki. Based on a
method supplied by Takeda Chemical Industry Co. Ltd. Japan.
17
BENSULTAP 464
2.2 Infrared. Prepare potassium bromide discs from the sample and from
bensultap analytical standard using 1.5 mg material and 150 mg potassium
bromide. Scan the discs from 4000 to 650 cm-1. The spectrum produced from
the sample disc should not differ significantly from that for the standard.
2.3 Colorimetry. Weigh about 50 mg of the sample and dissolve in 50 ml of
methanol. Pipette into a glass-stoppered Erlenmeyer flask (50 ml) 1 ml of this
solution, add 4 ml of methanol and 1 ml of 10% ammonia test solution, mix well
and allow to stand for 5 minutes. Add 1 ml of 5% sodium tetrahydroborate test
solution and add 1.2 ml of diluted hydrochloric acid (1+1). Blow out the
evolving hydrogen gas with air completely. Add 0.5 ml of 10% ammonia test
solution and 1 ml of 0.05% DTNB solution. This solution immediately changes
to deep yellow.
3 Bensultap
OUTLINE OF METHOD Bensultap is dissolved in acetonitrile and determined
by reserved phase high performance liquid chromatography with UV detection.
REAGENTS
Acetonitrile HPLC grade. Filter through a 0.45 µm filter.
Water HPLC grade. Filter through a 0.45 µm filter.
Eluant Mix acetonitrile (600 ml) and water (400 ml) and degas before use
Bensultap analytical standard of known purity
Calibration solution Weigh (to the nearest 0.1 mg) about 100 mg (s mg)
bensultap analytical standard into a 100 ml volumetric flask. Dissolve in
acetonitrile (90ml), make up to volume with acetonitrile, and mix thoroughly.
Pipette 10.0 ml of this solution into a 100 ml volumetric flask and make up to
volume with acetonitrile. Keep the solution in a thermostated bath if the room
temperature varies by more than ± 1°C. Filter the solution through a 0.45 µm
filter before injection. Prepare a fresh stock solution of bensultap daily.
5,5-Dithiobis(2-nitrobenzoic acid) DTNB
DTNB solution Weigh into a 100 ml volumetric flask 50 mg DTNB. Dissolve in
methanol, dilute to volume, and mix.
APPARATUS
High performance liquid chromatograph equipped with a constant flow pump, a
loop injector, a thermostated column oven and a 254 nm UV detector
Column stainless steel, 250 × 4.0 (i.d.) mm, packed with NUCLEOSIL® C18
(Macherey-Nagel)
Electronic integrator
Recorder
18
BENSULTAP 464
Ultrasonic bath
Filter assembly Gelman or equivalent with a 0.45 µm filter
PROCEDURE
(a) Operating conditions (typical)
Flow rate 1.0 ml/min
Oven temperature 40 ± 1 °C
Detector wavelength setting 254 nm
Detector sensitivity 8 × 10-2 (AUFS)
Injector volume 10 µl
Chart speed 5 mm/min
Retention time bensultap: about 7.5 min
(b) Preparation of sample solution Weigh (to the nearest 0.1 mg) enough sample
(w mg) to contain about 100 mg bensultap into a 100 ml volumetric flask.
Dissolve in acetonitrile (90 ml), make up to volume with acetonitrile, and mix
thoroughly. Pipette 10.0 ml of this solution into a 100 ml volumetric flask and
make up to volume with acetonitrile. Filter the solution through a 0.45 µm filter
before injection.
(c) Determination Inject 10 µl aliquots of the calibration solution until the
response factor varies by less than 1% for successive injections. Then inject in
duplicate 10 µl aliquots of the sample solution followed by an injection of the
calibration solution. Determine the peak area (Hw) either by automatic integrator
or by the manual procedure measuring peak height.
(d) Calculation Determine the response factor (f) from the peak area (Hs) of the
calibration solution injections preceding and following the two sample
injections. Average these values. The response factor is:
Hs
f
s
where:
Hs = peak area of bensultap in the calibration solution
s = mass of bensultap standard (mg)
The average response factor is:
f1 f2
fav
2
19
BENSULTAP 464
Hs P
Bensultap content
f av w
where:
Hw = peak area of bensultap in the sample solution
W= mass of sample taken (mg)
P= purity of bensultap standard (g/kg)
Repeatability r95 = 11.9 g/kg at 978 g/kg active ingredient content
Reproducibility R95 = 26.9 g/kg at 978 g/kg active ingredient content
BENSULTAP WETTABLE POWDERS
*
464/WP/M/-
1 Sampling. Take at least 500 g
2 Identity tests
2.1 HPLC. As for bensultap technical 464/TC/M/2.1.
2.2 Infrared. Extract the bensultap with acetonitrile, filter and evaporate the
solvent. Proceed as for bensultap technical 464/TC/M/2.2.
3 Bensultap
OUTLINE OF METHOD Bensultap is extracted with acetonitrile and
determined by reversed phase high performance liquid chromatography with UV
detection.
REAGENTS AND APPARATUS As for bensultap technical 464/TC/M/3
except:
(b) Preparation of sample solution. Weigh (to the nearest 0.1 mg) enough sample
(w mg) to contain about 100 mg bensultap into a 100ml Erlenmeyer flask with
stopper. Pipette 50.0 ml of acetonitrile into the flask and shake for 20 minutes.
Transfer this solution to a suitable centrifugal tube and centrifuge for 10 minutes
at 3000 rpm. Pipette 5.0 ml of the upper clear solution into a 100 ml volumetric
flask and make up to volume with acetonitrile. Mix thoroughly.
*
CIPAC method 1991. Prepared by the Japanese Committee (JAPAC). Chairman: Dr. T Suzuki. Based on a
method supplied by Takeda Chemical Industry Co. Ltd. Japan.
20
BENSULTAP 464
Repeatability r95 = 10.3 g/kg at 513 g/kg active ingredient content
Reproducibility R95 = 18.2 g/kg at 513 g/kg active ingredient content
4 Suspensibility (Draft method)
(a) Preparation of suspension. MT 15.1 (i)
(b) Determination of sedimentation. MT 15.1 (ii)
(c) Determination of bensultap in the bottom 25 ml of suspension. After removal
of the top 225 ml of suspension, add exactly 10 ml of chloroform to the 25 ml
remaining in the cylinder and mix well. Transfer the solution in the cylinder to a
suitable centrifugal tube and centrifuge. Determine the bensultap concentration
in the chloroform solution using the HPLC method.
BENSULTAP EMULSIFIABLE CONCENTRATES
*
464/EC/ M/-
1 Sampling. Take at least 500 ml.
2 Identity test
HPLC. As for bensultap technical 464/TC/M/2.1
3 Bensultap As for bensultap technical 464/TC/M/3.
Repeatability r95 = 8.4 g/kg at 257 g/kg active ingredient content
Reproducibility R95 = 16.4 g/kg at 257 g/kg active ingredient content
BENSULTAP SUSPENSION CONCENTRATES
*
464/SC/M/-
1 Sampling. Take at least 500 ml.
2 Identity test
HPLC. As for bensultap technical 464/TC/M/2.1
3 Bensultap As for bensultap technical 464/TC/M/3 except:
(b) Preparation of sample solution. Thoroughly shake the sample container to
assure that the suspension in homogenous. Immediately weigh (to the nearest
0.1 mg) enough sample (w mg) to contain about 100 mg bensultap into a 100 ml
volumetric flask. Proceed as for bensultap technical 464/TC/M/3 (b) beginning
at: "Dissolve in acetonitrile ... etc."
*
CIPAC method 1991. Prepared by the Japanese Committee (JAPAC). Chairman: Dr. T Suzuki. Based on a
method supplied by Takeda Chemical Industry Co. Ltd. Japan.
21
BENSULTAP 464
Repeatability r95 = 8.4 g/kg at 257 g/kg active ingredient content
Reproducibility R95 = 16.4 g/kg at 257 g/kg active ingredient content
4 Suspensibility (Draft method)
(a) Preparation of suspension and determination of sedimentation. MT 161.
(b) Determination of bensultap in the bottom 25 ml of suspension. As for
bensultap wettable powders 464/WP/M/4.
BENSULTAP DUSTABLE POWDERS
*
464/DP/M/-
1 Sampling. Take at least 1 kg
2 Identity tests
2.1 HPLC. As for bensultap technical 464/TC/M/2.1.
2.2 Infrared. Extract the bensultap with acetonitrile. Filter and evaporate the
solvent. Proceed as for bensultap technical 464/TC/M/2.2.
3 Bensultap
OUTLINE OF METHOD Bensultap is extracted with acetonitrile and
determined by reversed phase high performance liquid chromatography with UV
detection.
REAGENTS AND APPARATUS As for bensultap technical 464/TC/M/3
DETERMINATION As for bensultap technical 464/TC/M/3 except:
(b) Preparation of sample solution. Weigh (to the nearest 0.1 mg) enough sample
(w mg) to contain about 100 mg bensultap into a 100 ml Erlenmeyer flask with
stopper. Pipette 50.0 ml of acetonitrile into the flask place in an ultrasonic bath for
3 minutes, and shake for 20 minutes. Transfer this solution to a suitable centrifugal
tube and centrifuge for 10 minutes at 3000 rpm. Filter the upper solution through a
0.45 µm filter, pipette 5.0 ml of the filtrate into a 100 ml volumetric flask, and
make up to volume with acetonitrile. Mix thoroughly.
Repeatability r95 = 1.3 g/kg at 22 g/kg active ingredient content
Reproducibility R95 = 1.6 g/kg at 22 g/kg active ingredient content
*
CIPAC method 1991. Prepared by the Japanese Committee (JAPAC). Chairman: Dr. T Suzuki. Based on a
method supplied by Takeda Chemical Industry Co. Ltd. Japan.
22
