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Luliconazole Specs and STP - From DMF - Nosch Labs
Luliconazole Specs and STP - From DMF - Nosch Labs
Luliconazole Specs and STP - From DMF - Nosch Labs
3.2.S.4.1 SPECIFICATION
3.2.S.4.1 SPECIFICATION
Note:
1.0 Description:
Spread the material in thin layer in Petri dish and view it transversely from top under
illuminated light and conclude.
2.0 Solubility:
Weigh accurately about 1.0 gm of sample dissolve in 10 to 30 mL of Methanol, the
resulting solution should be clear.
Weigh accurately about 1.U gm of sample dissolve in IN to 3U inL of‘ Acetone, the
resulting solution should be clear.
Weigh accurately about 0.1 gm of sample dissolve in 10 to 100 mL of Ethanol, the
resulting solution should be clear.
Weigh accurately about 10 ing of sample dissolve in 100 mL of Water, the resulting
solution should not be clear.
View transversely from top under illuminated light and conclude.
3.0 Identification:
3.1 By IR:
Standar d }ireparation:
Take about 300 to 400 mg of potassium bromide (previously dried) in mortar and grind
it to a fine powder. Add about 1 to 2 mg of Luliconazole working standard and again
grind to fine powder, Mix well the contents. Clean the die and it components with
tissue paper. Carefully place on the pellet (polished face in upside position) into the
bore of the cylinder. Using a butter paper transfer the fine powder sample (grinded with
potassium bromide) in the bore of the cylinder. Tape the side of die gently so that the
powder is evenly distributed across the face of the polish face. Insert the second pellet
with police facing down.
Place the die assembly under “hydraulic press “Evacuate die assembly. Then apply
pressure about 6 to 8 tons to the plunger to produce transparent disc. After about 3
minutes remove die base from cylinder leaving plunger in released position. Put
cylinder bore below the cylinder and place them “hydraulic press” Apply pressure
across the plunger until the pellet immersed from the cylinder followed by disc.
Remove the disc carefully and put into the sample compartment of the instrument.
Record the spectrum of standard preparation from 4000 - 650 cm c
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Sample preparation:
Take about 300 to 400 mg of potassium bromide and about 1 to 2 mg of sample prepare
the pellet following the standard pellet preparation method.
The infrared absorption spectrum of the sample exhibits maxima only at same
wavelengths as that of a similar preparation of the corresponding reference/working
standard.
Note: If the pellet is not transparent it should be remade.
3.2 By HPLC:
Refer the cloomatograins of standard and test obtained under the test for assay.
Compare the chromatograms of standard with test solutions for retention time of
principal peak.
4.0 Loss on drying:
Weigh empty stopper shallow bottle previously dried at l05°C for 30 min, weight taken
as a (W i ) Transfer about 1.0 gin of sample and cover the bottle with stopper, weight
taken as a (W,). The sample is distributed as evenly as practicable by gentle, sidewise
shaking. The loaded bottle is allowed to dry at 105°C for 3 hours under vacuum. While
drying the bottle is kept open leaving the stopper in the oven.
After drying, the bottle is taken out along with stopper, cool in desiccators, weigh the
bottle and recorded the weight, weight taken as a (W3)
Calculation:
Where,
Wt (gm)
Weight of glass- stoppered bottle in grams.
Wt (gm)
— Weight of glass- stoppered bottle with sample before drying.
W3 (
= Weight of glass- stoppered bottle with sample after drying.
)
(If the amount of the residue so obtained exceeds the prescribed limit, repeat the
moistening with sulphuric acid and ignition, as previously for 30 min period until two
consecutive weighing do not differ by more than 0.5 ing or until the percentage of
residue complies with prCscribed limit).
Calculation:
W3 — W 1
Residue on ignition = ----------------- ^ 100 = O
O W W.
W, — W,
Where,
i (W) — Weight of the empty crucible.
W2
= Weight of the crucible with sample before moistening.
(gin) = Weight of the crucible with residue after ignition.
W3 ( )
Test Preparation:
Transfer about 1.0 gin of the sample in a silica crucible, add sufficient sulphuric acid to
wet the sample, and carefully ignite at a low temperature until thoroughly charred. (The
crucible may be loosely covered with a suitable lid during charring.). Add to the
carbonized mass 2 rnL of nitric acid and 5 drops of sulphuric acid, and heat cautiously
until white fumes no longer are evolved. Ignite, preferably in a muffle furnace, at
500°C to 600°C, until the carbon is completely burned off. Coo1, add 4 mL of 6N
hydrochloric acid cover, digest on steam bath for 15 minutes, uncover, and slowly
evaporate on a steam bath to dryness. Moisten the residue with 1 drop of hydrochloric
acid, add 10 mL of hot water, and digest for 2 minutes. Add 6 N ammonium hydroxide
drop wise, until solution in just alkaline to litmus paper, dilute with water to 25 mL,
and Adjust with lN acetic acid or 6N Ammonium hydroxide to a pH between 3.0 and
4.0, using short-range pH indicator paper as an external indicator. Filter if necessary,
rinse the crucible and the filter with 10 mL of water, combine the filtrate and rinsing in
a 50 mL colour-comparison tube, dilute with water to 40 mL, and mix.
Procedure:
To each of the tubes containing the standard preparation and the test preparation, add 2
mL of pH 3.5 acetate buffer, and then add 1.2 mL of Thioacetamide-glycerin base TS,
dilute with water to 50 mL, mix, allow to stand for 2 minutes and view downward over
a white surface.
Observation:
The colour of the solution from the test preparation is not darker than that of the
solution from the standard preparation.
Mobile phase:
Mix n-Hexane and Isopropyl alcohol and Ethanol in ratio of 650:50:300
(v/v/v). Diluent:
Mix n-I3exane and Ethanol in the ratio of 60:40
(v/v). Preparation of Blank solution:
Use diluent as a blank.
Preparation of reference solution (a):
Weigh accurately about 5.0 ing of Stereochemical purity of each standard (Isomer-1,
Isomer-2 and Isomer-3) transfer in to a 50 inL volumetric flask, Add 25 to 30 mL of
diluent and sonicate to dissolve. Make up to the mark with diluent and mix well.
Preparation of reference solution (b):
Weigh accurately about 50.0 mg of Luliconazole working standard, transfer in to a
50 mL volumetric flask, Add 25 to 30 mL of diluent and sonicate to dissolve. Add 2
mL of reference solution (a) into it. Make up to the mark with diluent and mix well.
Preparation of reference solution (c):
Weigh accurately about 20.0 mg of Luliconazole working standard, transfer in to a
20 mL volumetric flask, Add 10 to 15 mL of diluent and sonicate to dissolve. Make
up to the mark with diluent and mix well.
Dilute 5.0 mL of this solution to 50 mL with diluent and mix well.
Further dilute 1 mL of this solution to 100 mL with diluent and mix
well.
Procedure:
.4fter equilibrating the column separately inject the single injection of blank solution,
reference solution (b), six replicate injections of refercnce solution (c) and each of
test solution once in the liquid Cliroinatograph. Record the response eliminating the
peak due to blank. Integrate only isomer peak and main peak.
066
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The retention time of the main peak is about 16 ruin under this condition.
System suitability parameters:
1. The relative standard deviation determined from the reference solution (c) in six
replicated injections should be not more than 5.0%.
2. Resolution between the isomer -1 and Isomer-2 from reference solution (b) should be
not less than 1.3
3. Resolution between the Isomer-2 and main peak from reference solution (b) should
be not less than 1.5
4. Tailing factor of main peak from reference solution (b) should be not more than 2.0
Relative retention time and Response factor Isomer-1, Isomer-2, Isomer-3 and
Luliconazole:
S. No Name Relative retention time Response factor (RF)
1. Isomer-1 0.79 1.13
2. Isomer-2 0.89 1.04
3. Isomer-3 2.17 0.83
4. Luliconazole 1.0
Calculation:
AT Ws 5 1 20 P
-- ------- ------ ------- ------ ------- RF •100 = 00
As 20 50 100 WT 100
Where,
AT Average area of respective isomer in test solution.
As = Average area of Luliconazole in reference solution
(c).
We Weight of the standard in reférence solution (c).
WT ' Average weight of sample in test solution.
P — Potency of Luliconazole working standard.
RF — Response factor of respective isomer.
Buffer:
k4ix 1.0 mL of Perch1oñ.c acid in 1005 mL of v°ater.
Mobile phase-B:
lxlix buffer, acetonitrile and methanol in the ratio of 20:70:10 (v/v’v).
Further dilute to 1 mL of this solution to 100 inL with diluent and mix well.
Relative retention time and Response factor of known impurity and Luliconazole:
Response
SNo. Name Relative retention time
factor(RF)
Impurity-A 0.75 1.57
2. Z-Isomer. 0.88
3. Luliconazole 1.0 1 1.0
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Calculation:
For Impurity-A:
AT . US 5 1 100 P
0
------- 0x ------- x ----- x ------- x ------- x ------- 1.57 100 =
As 100 50 100 IT 100
Where,
AT Average area of impurity-A in test solutioi:.
Ws = Weight of standard in reference solution (a).
As Average area of principal peak in reference solution (b).
IT ' Weight of sample in test solution.
P = PotcncJ of Luliconazole -WO7king standard.
Diluent:
Mix water and acetonitrile in the ratio of 20:80 (v/v).
071
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Calculation:
AT US 5 100 50 P 100
------x-------x-----x-------x-------x------x 100= %w/w.
As 100 50 IT 5 100 (100-LOD)
\Vhere,
AT Average area of sample in test solution.
Ws = Weight of standard in standard solution.
As — Average area of principal peak in standard solution.
W — Weight of sample in test solution.
T = Potency of Luliconazole working standard.
P Loss on drying in the sample.
LOD
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Procedure:
After equilibrating the column, separately inject the equal volume of blank solution
in once, six replicate injections of reference solution (b) and then inject test solution
in once into the liquid chromatograpli. Integrate only peak to Dimethyl sulfoxide.
The retention time of Dimethyl sulfoxide is about 4.5 min under these conditions.
System suitability parameter:
1. The relative standard deviation determined from the reference solution (b) in six
- replicate injections should not be more than 5.0 %.
2. Tailing factor of the Dimethyl sulfoxide from reference solution (b) should not
be more than 2.0.
Calculation:
AT Ws 5 20 P
------------x-----------x-----------x------------x ------- --- 10‘ = pm.
As 100 100 WT 100
Where,
AT = Average Area of in dimethylsulfoxide in test solution.
As = Average area of dimethylsulfoxide in reference solution (b).
+'s \Veight of Dimethyl sulfoxide standard in rcference solution
(a). WT - Weight of sample in test solution.
P = Potency of dimetliylsulfoxide standard.
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PART-I:
Instrument Gas chromatograph equipped with
flame ionization detector and head
Chromatographic parameters: space.
Column
Column temperature DB-1,60in x 0.32mm, 5.0 pin.
40°C (hold for 10 minutes) to 240 C
Injector temperature @ 20° C /minute (hold for 18
minutes)
Detector temperature
200°C
Carrier gas
270°C
Linear velocity
Nitrogen
Pressure rarnp
20 cm/sec
Split ratio 10.9 psi (hold for 25 iTrinutes) to 18 psi
@ 7 psi/minute (Hold at l8psi for 12
Headspace parameter's: minutes)
Incubation temperature 10:1
Incubation time
Agitation speed 85°C
Syringe temperature l5minutes
Injection volume 600 rpm
115°C
1.0 mL
Standard Solution should be prepared freshly for every analysis.
Diluent:
Benzyl alcohol.
Preparation of blank solution:
Take 2.0mL of Benzyl alcohol in a 20mL Headspace vial.
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Procedure:
Separately inject equal volumes of the blank solution in once, Tetrahydrofuran
standard solution in once, hexane standard solution in once, standard solution (six
injections), blank in once and the sample solution in once from each preparation into
the system, record the chromatograin, measure the peak responses and calculate the
amount of residual solvent present in sample.
076
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Disregard the peak due to blank and Dimethyl sulfoxide (Retention time is about
25.81 minutes).Order of elution taken from standard is Methanol, Acetonitrile,
Acetone, Isopropyl alcohol, Methylene chloride, Ethyl acetate and Toluene. Confirm
the retention time of Hexane fraction by injecting the hexane standard. Confirm the
retention time of Tetrahydrofuran faction by injecting the Tetrahydrofuran standard.
System suitability:
The relative standard deviation (RSD) for each solvent peak response (area) must be
less than 15 % from replicate injections of standard solution.
Calculation:
AT V S ^ Ds 5
2
10 = ppm.
As 50 100 WT 100
Where,
P T = Area of respective solvent in sample solution.
Ds Density of respective solvent.
Vt — Volume of respective solvent in standard solution (in
qL).
As = Average area respective solvent in standard solution.
WT“ — Weight of sample in mg.
P = Purity of respective solvent.
PART-II:
FOR TRIETHYLAMINE:
Chromatographic parameters:
Instrument Gas chromatograph equipped with
flame ionization detector and
Headspace.
Column
RTX-5 Amine, 30 x 0.53mmID,3.Ohm
Column temperature
40°C (hold for 5 minutes) to 240°C @ 40° C
/minute (hold for 10 minutes)
Injector temperature
250°C
Dctector temperature
300°C
Carrier gas
Nitrogen
Linear velocity
35 cm/sec
Split ratio
40: l
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Headspace parameters:
Incubation temperature 95°C
Incubation time l5minutes
Agitation speed 600 rpm
Syringe temperature 115°C
Injection volume 1.0 mL
Diluent Dimethyl sulfoxide.
Preparation of blank
solution:
Take 5.0 mL of Dimethyl sulfoxide in 20 inL head space vial, containing about 500
mg of sodium carbonate anhydrous.
Preparation of standard stock solution:
Take 17.5)L of Trietliylainine into a 100 mL of volumetric flask containing 50-60
iiiL of Dimethyl sulfoxide and make up to the mark with Dimethyl sulfoxide and
mix.
Preparation of Standard solution:
Take 5.0 mL of Standard stock solution in a 100 mL volumetric flask and dilute up to
the mark with Dimethyl sulfoxide.
Take 5.0 UL of the standard solution in 6 different 20 mL headspace vial containing
500 mg of sodium carbonate anhydrous.
Note: Standard solution should be prepared freshly for every analysis.
Preparation of sample solution:
Weigh about 100 mg of sample in 20 mL Head space vial, containing about 500 ing
of sodium carbonate anhydrous and add 5.0 mL of Dimethyl Sulfoxide. (Prepare in
duplicate).
Procedure:
Separately inject equal volumes of blank solution in once, standard solution in six
injections, blank in duplicate and the sample solution in once from each preparation
into the system, record the chromatograms.
Disregard the peaks other than Triethylamine and measure the peak responses of
Triethylainine. Integrate only Triethylamine peak.
Note: Inject two blanks after standard solution of system suitability to avoid the carry
over in sample.
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suitability:
1. The relative standard deviation for each solvent peak response (area) must be
less than 15 % from replicate injections of standard solution.
Calculation:
AT VS x Ds 5 5 P
---- x ------------ x --------- x -------- x --------- x 10‘ = pm.
AS 1 100 WT 100
Where,
AT ' Area of triethylainine in sample solution.
Ds = Density of triethylainine.
Vs = Volume of triethylamine in standard solution (in
qL).
As = Average area trietliylamine in standard solution.
WT — Weight of sample in nag.
P = Purity of triethylainine.