THIABENDAZOLE 323

THIABENDAZOLE
323

N
S

N N
H

ISO common name Thiabendazole

Chemical name 2-(Thiazol-4-yl)benzimidazole (IUPAC);
2-(4-thiazolyl)-1H benzimidazole (CA; 148-79-8)
Empirical formula C10H7N3S
RMM 202.2
m.p. 304-305 °C (sublimes above 250 °C)
v.p. Non volatile at room temperature
Solubility In water: about 25 mg/l between pH 3 and pH 5 at
25 °C, 10 g/l at pH 2; in acetone 4.2 g/l; ethanol
7.9 g/l; ethyl acetate 2.1 g/l; benzene 0.23 g/l;
chloroform 80 mg/l; dimethyl formamide 39 g/l;
dimethyl sulfoxide 80 g/l; methanol 9.3 g/l.
Description Colourless crystals
Stability Under normal conditions stable to hydrolysis, light
and heat
Formulations Wettable powders, dustable powders soluble liquids
and suspension concentrates

THIABENDAZOLE TECHNICAL
*
323/TC/M/-

1 Sampling. Take at least 100 g.

2 Identity tests
2.1 HPLC. Use the HPLC method below. The retention time of thiabendazole
for the sample solution should not differ by more than 1% from that for the
standard.

*
CIPAC method 1992. Prepared by DUPAC.
Based on a method supplied by Merck, Sharp & Dohme.

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 THIABENDAZOLE 323

2.2 IR. Prepare potassium bromide discs from the sample and from pure
thiabendazole using about 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.

3 Thiabendazole
OUTLINE OF METHOD The sample is dissolved in methanol and the content
of thiabendazole is determined by reversed phase liquid chromatography using
external standardization and an ammonium acetate-methanol solution as mobile
phase.

REAGENTS

Methanol HPLC quality

Ammonium acetate
Acetic acid glacial
Thiabendazole standard of known purity
Mobile phase ammonium acetate solution (pH 3)/methanol 50 + 50 v/v.
Dissolve ammonium acetate (0.77 g) in water (100 ml), add acetic acid (25 ml)
and dilute to 1 l with water. Mix 500 ml of the buffer solution with 500 ml
methanol. Degas under vacuum for 10 min.
Calibration solution. Weigh (to the nearest 0.1 mg) about 100 mg pure
thiabendazole (s mg) into a volumetric flask (100 ml). Dissolve in methanol and
fill to the mark with methanol. Mix well. Transfer by pipette 5.00 ml of this
solution to a volumetric flask (100 ml) and fill to the mark with mobile phase.
Filter through a 0.45 µm filter before injection.

APPARATUS

Liquid chromatograph equipped with a variable wavelength UV detector and an

electronic integrator
Chromatographic column 300 × 3.9 (i.d.) mm packed with µ-Bondapack C18,
10 µm

PROCEDURE

(a) Operating conditions (typical)

Column dimensions 300 × 3.9 (i.d.) mm
Packing µ-Bondapack C18, 10 µm
Mobile phase ammonium acetate solution (c = 0.01 mol/l)/
methanol 50+50 (v/v)
Wavelength setting 302 nm

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Column temperature ambient

Injection volume 10 µl
Flow rate 1.5 ml/min
Chart speed 0.5 cm/min
Retention time thiabendazole: about 4 min

(b) System suitability check. Make repetitive injections (10 µl) of the calibration
solution until the response is stable and the thiabendazole peak areas for
successive injections agree within ± 1% of their mean. Two small peaks of
impurities should appear after, and well separated from the thiabendazole peak.

Calculate the tailing factor (T) by the formula:

a b
T
2a

a = distance of the leading edge of the peak to the peak centre measured
at 5% of the peak height
b = distance of the tailing edge of the peak to the peak centre measured
at 5% of the peak height
If the tailing factor is more than 2 replace the column.

(c) Preparation of sample. Weigh (to the nearest 0.1 mg) into a volumetric flask
(100 ml) enough sample to contain about 100 mg thiabendazole (w g). Dissolve
in methanol and fill to the mark with methanol. Mix well. Transfer by pipette
5.00 ml of this solution to a volumetric flask (100 ml) and fill to the mark with
mobile phase. Filter the solution through a 0.45 µm filter before injection.
(d) Determination. Inject a 10 µl portion of the calibration solution. Then make
two injections of the sample solution followed by another injection of the
calibration solution. Proceed in the same way for other sample solutions.
Measure the peak areas and average the peak areas of the calibration solution
preceding and following the injection of the sample solution. Average also the
peak areas of the two successive sample solutions.
(e) Calculation

Hw s P
Thiabendazole content g/kg
Hs w

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

Repeatability r = 27 g/kg at 989 g/kg active ingredient content

Reproducibility R = 30 g/kg at 989 g/kg active ingredient content

THIABENDAZOLE WETTABLE POWDERS

*
323/WP/M/-

1 Sampling. Take at least 500 g.

2 Identity tests. As for thiabendazole technical 323/TC/M/2.

3 Thiabendazole. As for thiabendazole technical 323/TC/M/3 except:

(a) Preparation of sample. Weigh (to the nearest 0.1 mg) into glass stoppered
conical flask (200 ml) enough sample to contain about 100 mg thiabendazole
(w mg). Add by pipette 100.0 ml methanol and stir for 30 min on a magnetic
stirrer. Let settle any solid material and transfer by pipette 5.00 ml of the
clear supernatant solution to a volumetric flask (100 ml). Fill to the mark with
mobile phase. Filter the solution through a 0.45 µm filter before injection.

Repeatability r = 10 g/kg at 590 g/kg active ingredient content

Reproducibility R = 11 g/kg at 590 g/kg active ingredient content

4 Suspensibility (Draft method)

REAGENTS AND APPARATUS As for MT 15 and for 323/TC/M/3.

PROCEDURE

(a) Preparation of suspension MT 15.1 (i).

(b) Determination of sedimentation MT 15.1 (ii).

*
CIPAC method 1992. Prepared by DUPAC.
Based on a method supplied by Merck, Sharp & Dohme.

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 THIABENDAZOLE 323

(c) Determination of thiabendazole in the bottom 25 ml of suspension. After

removal of the top 225 ml of suspension add methanol (about 200 ml), mix well
and place the cylinder in an ultrasonic bath for 15 min. Allow to cool to room
temperature and make up to the volume of 250 ml with methanol. Mix well.
Centrifuge or filter the suspension to remove inert ingredients. Transfer by
pipette 5.0 ml of the clear solution to a volumetric flask (100 ml), fill to the
mark with mobile phase, and mix well. Use this solution for the final analysis
according to method 323/TC/M/3.
(d) Calculation

111 ( c - Q )
Suspensibility = %
c

where:
c = mass of thiabendazole in the sample taken for the preparation of the
suspension (g).
Q = mass of thiabendazole in the bottom 25 ml of suspension

THIABENDAZOLE DUSTABLE POWDERS

*
323/DP/M/-

1 Sampling. Take at least 1 kg.

2 Identity tests. As for thiabendazole technical 323/TC/M/2.

3 Thiabendazole. As for thiabendazole technical 323/TC/M/3 except:

(c) Preparation of sample. Weigh (to the nearest 0.1 mg) into a glass-stoppered
conical flask (200 ml) enough sample to contain about 100 mg thiabendazole
(w mg). Add by pipette 100.0 ml methanol and stir for 30 min on a magnetic
stirrer. Centrifuge a portion of the solution at a speed of 3000 rpm. Transfer by
pipette 5.00 ml of the clear supernatant to a volumetric flask (100 ml) and fill to
the mark with mobile phase. Filter the solution through a 0.45 µm filter before
injection.

Repeatability r = 0.9 g/kg at 18.2 g/kg active ingredient content

Reproducibility R = 1.2 g/kg at 18.2 g/kg active ingredient content

*
CIPAC method 1992. Prepared by DUPAC.
Based on a method supplied by Merck, Sharp & Dohme.

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 THIABENDAZOLE 323

THIABENDAZOLE SOLUTIONS
*
323/SL/M/-

1 Sampling. Take at least 500 ml.

2 Identity tests. As for thiabendazole technical 323/TC/M/2.

3 Thiabendazole. As for thiabendazole technical 323/TC/M/3.

Repeatability r = 7.8 g/kg at 199 g/kg active ingredient content

Reproducibility R = 9.6 g/kg at 199 g/kg active ingredient content

THIABENDAZOLE SUSPENSION CONCENTRATES

*
323/SC/M/-

1 Sampling. Take at least 1 l. Shake the sample at least 1 min before sampling.

2 Identity tests. As for thiabendazole technical 323/TC/M/2.

3 Thiabendazole. As for thiabendazole technical 323/TC/M/3 except:

(c) Preparation of sample. Weigh (to the nearest 0.1 mg) into a volumetric flask
(100 ml) enough sample to contain about 100 mg (w mg) thiabendazole. Add
water (5 ml) and swirl to disperse the sample. Dilute to volume with methanol
and stir on a magnetic stirrer for 30 min. Transfer by pipette 5.0 ml of this
solution to a volumetric flask (100 ml) and fill to the mark with mobile phase.
Filter the solution through a 0.45 µm filter before injection.

Repeatability r = 6.4 g/kg at 410 g/kg active ingredient content

Reproducibility R = 13 g/kg at 410 g/kg active ingredient content

4 Suspensibility (Draft method)

REAGENTS AND APPARATUS As for MT 15 and for 323/TC/M/3.

*
CIPAC method 1992. Prepared by DUPAC.
Based on a method supplied by Merck, Sharp & Dohme.

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 THIABENDAZOLE 323

PROCEDURE

(a) Preparation of suspension and determination of suspension MT 161.

(b) Determination of thiabendazole in the bottom 25 ml of suspension. As for
thiabendazole wettable powders 323/WP/M/4 (c).
(c) Calculation As for 323/WP/M/4 (d).

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