Accessed from 59.99.44.

69 by universetx608 on Sat May 05 02:33:19 EDT 2018

USP 41 Official Monographs / Atorvastatin 391

System suitability rT = sum of all the peak responses from the Sample
Sample: Standard solution solution
Suitability requirements Acceptance criteria: See Table 1.
Tailing factor: NMT 2.0
Relative standard deviation: NMT 1.4% Table 1
Analysis
Samples: Standard solution and Sample solution Relative Acceptance
Calculate the percentage of the labeled amount of Retention Criteria,
atomoxetine (C17H21NO) dissolved: Name Time NMT (%)
Desmethyl atomoxetinea 0.76 0.3
Result = (rU/rS) × (CS/L) × V × 100
.

Atomoxetine 1.0 —
Atomoxetine
rU = peak response from the Sample solution
N-amideb 1.2 0.2
rS = peak response from the Standard solution .

CS = concentration of atomoxetine in the Standard Any individual

solution (mg/mL) unspecified degradation —
L = label claim (mg/Capsule) product 0.2
V = volume of Medium (mL) Total impurities — 1.0
Tolerances: NLT 80% (Q) of the labeled amount of a. (R)-N-Methyl-3-phenoxy-3-phenylpropan-1-amine.
atomoxetine (C17H21NO) is dissolved. b (R)-1-Methyl-1-[3-phenyl-3-(o-tolyloxy)propyl]urea.
• UNIFORMITY OF DOSAGE UNITS 〈905〉: Meet the
.

requirements ADDITIONAL REQUIREMENTS

IMPURITIES
• ORGANIC IMPURITIES
Buffer: Dissolve 4.9 g of sodium 1-decanesulfonate and
6.9 g of monobasic potassium phosphate in 1 L of
water. Adjust with phosphoric acid to a pH of 3.1.
Mobile phase: Acetonitrile and Buffer (41:59)
Sensitivity solution: 0.1 µg/mL of atomoxetine in Mo-
• PACKAGING AND STORAGE: Preserve in well-closed contain-
ers. Store at controlled room temperature.
• USP REFERENCE STANDARDS 〈11〉
USP Atomoxetine Hydrochloride RS
.

bile phase Atorvastatin Calcium

System suitability solution: 1 mg/mL of atomoxetine
containing atomoxetine N-amide prepared as follows.
Weigh equal amounts of USP Atomoxetine Hydrochlo-
ride RS and urea, and place in a volumetric flask. Add
water to fill 10% of the final volume. Sonicate for 3
min. Place the flask in an 85° oven for 40 min. Allow
the solution to cool to room temperature. Dilute with

Mobile phase to volume. [NOTE—The oven temperature
and time in the oven can be adjusted to give a suitable
level of atomoxetine N-amide peak.]
Sample solution: 1 mg/mL of atomoxetine in Mobile
phase, from the contents of NLT 5 Capsules prepared as
follows. Transfer the Capsule contents to a suitable vol-
umetric flask. Fill 50% of the final volume with Mobile
phase. Swirl, and let stand for 15 min. Dilute with Mo-
bile phase to volume.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 215 nm
Column: 4.6-mm × 15-cm; 3.5-µm packing L7
Column temperature: 30°
Flow rate: 1 mL/min
Injection volume: 10 µL
Run time: 2.3 times the retention time of atomoxetine
System suitability
Samples: Sensitivity solution and System suitability
solution
[NOTE—See Table 1 for the relative retention times.]
Suitability requirements
Resolution: NLT 2.6 between atomoxetine and
atomoxetine N-amide, System suitability solution
Relative standard deviation: NMT 5%, Sensitivity
solution
Analysis
Sample: Sample solution
Calculate the percentage of each individual impurity in
the portion of Capsules taken:
Result = (rU/rT) × 100
rU = peak response of each individual impurity
from the Sample solution
USP Monographs
C66H68CaF2N4O10 1155.36
1H-Pyrrole-1-heptanoic acid, 2-(4-fluorophenyl)-β,δ-
dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(phenylami-
no)carbonyl]-, calcium salt (2:1), [R-
(R*,R*)]-;
Calcium (βR,δR)-2-(p-fluorophenyl)-β,δ-dihydroxy-5-isopro-
pyl-3-phenyl-4-(phenylcarbamoyl)pyrrole-1-heptanoate
(1:2);
[(3R,5R)-7-[3-(Phenylcarbamoyl)-5-(4-fluorophenyl)-2-isopro-
pyl-4-phenyl-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid,
calcium salt]
Anhydrous [134523-03-8].
C66H68CaF2N4O10 · 3H2O 1209.41
Trihydrate [344423-98-9].
C66H68CaF2N4O10 · C3H8O2
Propylene glycol solvate 1231.46
DEFINITION
Atorvastatin Calcium contains NLT 98.0% and NMT
102.0% of atorvastatin calcium (C66H68CaF2N4O10), calcu-
lated on the anhydrous and solvent-free basis. If labeled
as a propylene glycol solvate, it contains NLT 98.0% and
NMT 102.0% of atorvastatin calcium (C66H68CaF2N4O10),
calculated on the anhydrous, propylene glycol-free, and
solvent-free basis. It may contain a suitable antioxidant.
IDENTIFICATION
• A. INFRARED ABSORPTION 〈197K〉: [NOTE—If a difference ap-
pears in the IR spectra of the analyte and the standard,

Official from May 1, 2018

Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 59.99.44.69 by universetx608 on Sat May 05 02:33:19 EDT 2018

392 Atorvastatin / Official Monographs USP 41

separately dissolve equal portions of the sample specimen Suitability requirements

and the USP Reference Standard in equal volumes of
methanol, evaporate the solution to dryness in similar
containers under identical conditions, and repeat the test
on the residues.]
• B. CALCIUM
Diluent: Methanol, water, and hydrochloric acid
(75:25:2)
Sample solution: 0.05 mg/mL of Atorvastatin Calcium
in Diluent
Blank: Diluent
Analysis
Samples: Sample solution and Blank
Instrumental conditions
(See Atomic Absorption Spectroscopy 〈852〉.)
Mode: Atomic absorption spectrophotometry
Analytical wavelength: Calcium emission line at
422.7 nm
Flame: Air–acetylene
Acceptance criteria: The Sample solution exhibits a sig-
nificant absorption at the calcium emission line at 422.7
nm.
ASSAY
• PROCEDURE
Buffer: 3.9 g/L of ammonium acetate in water. Adjust
with glacial acetic acid to a pH of 5.0 ± 0.1.
Solution A: Acetonitrile, stabilizer-free tetrahydrofuran,
and Buffer (21:12:67)
Solution B: Acetonitrile, stabilizer-free tetrahydrofuran,
and Buffer (61:12:27)
Mobile phase: See Table 1. [NOTE—If necessary, adjust
the Mobile phase by increasing or decreasing the per-
centage of acetonitrile or the pH of the ammonium
acetate solution to achieve a retention time of 26–34
min for the atorvastatin peak.]
USP Monographs
Resolution: NLT 1.5 between the peaks for atorvasta-
tin related compound B and atorvastatin, System suit-
ability solution
Tailing factor: NMT 1.6, Standard solution
Relative standard deviation: NMT 0.6%, Standard
solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of atorvastatin calcium (C66H68
CaF2N4O10) in the portion of Atorvastatin Calcium
taken:
Result = (rU/rS) × (CS/CU) × 100
rU = peak response from the Sample solution
rS = peak response from the Standard solution
CS = concentration of USP Atorvastatin Calcium RS
in the Standard solution (mg/mL)
CU = concentration of Atorvastatin Calcium in the
Sample solution (mg/mL)
Acceptance criteria: 98.0%–102.0% on the anhydrous
and solvent-free basis. If labeled as a propylene glycol
solvate, 98.0%–102.0% on the anhydrous, propylene
glycol-free, and solvent-free basis.
OTHER COMPONENTS
• CONTENT OF PROPYLENE GLYCOL (if labeled as a propylene
glycol solvate)
Diluent: Dimethylsulfoxide
Standard solution: 0.125 mg/mL of propylene glycol in
Diluent
Sample solution: 2.5 mg/mL of Atorvastatin Calcium
(as propylene glycol solvate) in Diluent. Use sonication
as needed to achieve a complete dissolution.
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: GC

Table 1
Detector: Flame ionization
Time Solution A Solution B Column: 0.53-mm × 75-m; 3-µm coating of G43
(min) (%) (%) Temperatures
0 100 0 Injection port: 230°
40 100 0 Detector: 250°
Column: See Table 2.
70 20 80
85 0 100
Table 2
100 0 100
105 100 0 Hold Time at
115 100 0 Initial Temperature Final Final
Temperature Ramp Temperature Temperature
Diluent: N,N-dimethylformamide (°) (°/min) (°) (min)
System suitability solution: 0.05 mg/mL of USP 100 0 100 1
Atorvastatin Calcium RS and 0.06 mg/mL of USP 100 10 140 5
Atorvastatin Related Compound B RS in Diluent 140 30 225 3
Standard solution: 0.4 mg/mL of USP Atorvastatin Cal-
cium RS in Diluent. [NOTE—Use sonication if necessary.] Carrier gas: Helium
Sample solution: 0.4 mg/mL of Atorvastatin Calcium in Flow rate: 6.0 mL/min
Diluent. [NOTE—Use sonication if necessary.] Injection volume: 1 µL
Chromatographic system Injection type: Splitless, using a suitable inlet liner
(See Chromatography 〈621〉, System Suitability.) System suitability
[NOTE—If significant fronting of the peaks for atorvasta- Sample: Standard solution
tin related compound B and atorvastatin is observed, Suitability requirements
use the following diluent to prepare the Sample solu- Tailing factor: NMT 2.0
tion, the Standard solution, and the System suitability Relative standard deviation: NMT 5.0%
solution: acetonitrile, stabilizer-free tetrahydrofuran, Analysis
and water (1:1:2).] Samples: Standard solution and Sample solution
Mode: LC Calculate the percentage of propylene glycol in the por-
Detector: UV 244 nm tion of Atorvastatin Calcium as propylene glycol sol-
Column: 4.6-mm × 25-cm; 5-µm packing L7 vate taken:
Column temperature: 35°
Flow rate: 1.5 mL/min Result = (rU/rS) × (CS/CU) × 100
Injection volume: 20 µL
System suitability rU = peak response of propylene glycol from the
Samples: System suitability solution and Standard Sample solution
solution

Official from May 1, 2018

Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 59.99.44.69 by universetx608 on Sat May 05 02:33:19 EDT 2018

USP 41 Official Monographs / Atorvastatin 393

rS = peak response of propylene glycol from the Calculate the percentage of each of the atorvastatin re-
Standard solution lated compounds A, B, C, and D in the portion of
CS = concentration of propylene glycol in the Atorvastatin Calcium taken:
Standard solution (mg/mL)
CU = concentration of Atorvastatin Calcium (as Result = (rU/rS) × (CS/CU) × 100
propylene glycol solvate) in the Sample
solution (mg/mL) rU = peak response of the relevant atorvastatin
Acceptance criteria: 5.4%–7.3% related compound from the Sample solution
rS = peak response of the relevant atorvastatin
IMPURITIES related compound from the Standard solution
CS = concentration of the relevant atorvastatin
related compound in the Standard solution
Delete the following: (mg/mL)
•• HEAVY METALS CU = concentration of Atorvastatin Calcium in the
.

Sample solution (mg/mL)

Diluent: Methanol and water (9:1) Calculate the percentage of any other individual
Sample solution: Dissolve 250 mg of the sample in impurity in the portion of Atorvastatin Calcium taken:
30 mL of Diluent.
Standard lead solution: Prepare as directed in Heavy Result = (rU/rT) × 100
Metals 〈231〉.
Reference solution: Dilute 0.5 mL of the Standard lead rU = peak response of any other individual impurity
solution with Diluent to 30 mL. from the Sample solution
Blank solution: 20 mL of Diluent rT = sum of all the peak responses from the Sample
Monitor solution: Dissolve 250 mg of Atorvastatin Cal- solution
cium in 0.5 mL of the Standard lead solution, and dilute Acceptance criteria: See Table 3. Disregard any peak
with Diluent to 30 mL. observed in the blank; the reporting level for impurities
Analysis is 0.05%.
Samples: Sample solution, Reference solution, Blank solu-
tion, and Monitor solution Table 3
To each solution, add 2 mL of pH 3.5 Acetate Buffer
prepared as directed in Heavy Metals 〈231〉. Mix, add Relative Acceptance
to 1.2 mL of thioacetamide–glycerin base TS, and mix Retention Criteria,
immediately. Pass the solutions through a membrane Name Time NMT (%)
filter of 0.45-µm pore size. Compare the spots on the Atorvastatin related
filters obtained with the different solutions. The compound Aa . 0.8 0.3
brown color of the spot from the Sample solution is Atorvastatin related
not more intense than that of the spot from the Ref- compound Bb 0.9 0.3
erence solution. The test is invalid if the Reference solu-
.

Atorvastatin 1.0 —

USP Monographs
tion does not show a slight brown color compared to
Atorvastatin related
the Blank solution, or if the color of the Monitor solu-
compound Cc 1.2 0.3
tion is not at least as intense as the color of the Refer- .

ence solution. Atorvastatin related

Acceptance criteria: NMT 20 ppm• (Official 1-Jan-2018) compound Dd,e . . . 2.1 0.2
• ORGANIC IMPURITIES, PROCEDURE 1: [NOTE—On the basis of Any other individual
—
the synthetic route or of the solid state nature of the impurity 0.1
drug substance, perform either Procedure 1 or Procedure Total impuritiesf . — 1.0
2. Procedure 2 may be suitable when atorvastatin lactone, a Desfluoro impurity.
atorvastatin epoxy tetrahydrofuran analog, and atorvasta-
.

b 3S,5R Isomer.
tin acetonide are possible related compounds, and it may
.

c Difluoro impurity.
be suitable for an amorphous form of the drug
.

d Epoxide impurity.
substance.]
.

e Atorvastatin related compound D may undergo a conversion to its cyclic

Buffer, Solution A, Solution B, Mobile phase, Diluent,
.

hemiketal, which is a specified impurity listed in Table 5 in Organic Impuri-

System suitability solution, and Chromatographic
system: Proceed as directed in the Assay.
Standard solution: 1.5 µg/mL each of USP Atorvastatin
Related Compound A RS, USP Atorvastatin Related
Compound B RS, USP Atorvastatin Related Compound
ties, Procedure 2, as “atorvastatin epoxy tetrahydrofuran analog”. The cyc-
lic hemiketal of atorvastatin related compound D elutes about 1–2 min
before atorvastatin related compound D. Use the sum of the areas of the
two peaks as a peak response for atorvastatin related compound D in the
Standard solution and the Sample solution.
f This total does not include atorvastatin related compound E, as deter-
.

C RS, and USP Atorvastatin Related Compound D RS in
Diluent
Sample solution: 1 mg/mL of Atorvastatin Calcium in
Diluent. [NOTE—Use sonication if necessary.]
System suitability
Sample: System suitability solution
Suitability requirements
Resolution: NLT 1.5 between the peaks for atorvasta-
tin related compound B and atorvastatin
Analysis
Samples: Standard solution and Sample solution
Chromatograph the Standard solution, and identify the
components based on their relative retention times,
given in Table 3.
mined in the Enantiomeric Purity test.
• ORGANIC IMPURITIES, PROCEDURE 2
Buffer: pH 5.0 mixture of 0.045 M ammonium formate
and 0.0045 M ammonium acetate solutions, prepared
as follows. Weigh 2.84 g of ammonium formate and
0.35 g of ammonium acetate, and dissolve in 950 mL of
water. Adjust with 20% formic acid to a pH of 5.0, and
dilute with water to 1 L.
Solution A: Acetonitrile and Buffer (33:67)
Solution B: Acetonitrile
Solution C: Stabilizer-free tetrahydrofuran
Mobile phase: See Table 4. Return to original condi-
tions, and re-equilibrate the system.

Official from May 1, 2018

Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
 Accessed from 59.99.44.69 by universetx608 on Sat May 05 02:33:19 EDT 2018

394 Atorvastatin / Official Monographs USP 41

Table 4 Table 5
Time Solution A Solution B Solution C Relative Relative Acceptance
(min) (%) (%) (%) Retention Response Criteria,
0 91 0 9 Name Time Factor NMT (%)
15 91 6 3 Atorvastatin
20 82 16 2 diaminoa . 0.58 0.74 0.15
25 82 16 2 Atorvastatin related
compound Ab 0.86 1.0 0.3
50 32 66 2
.

Atorvastatin related
55 32 66 2
compound Bc . 0.94 1.0 0.3
Diluent: Acetonitrile, stabilizer-free tetrahydrofuran, and Atorvastatin 1.0 — —
Buffer (60:5:35) Atorvastatin related
Peak identification solution: 0.5 mg/mL of USP compound Cd (if .

Atorvastatin Calcium RS and 2.5 µg/mL each of USP present) 1.1 1.0 0.3
Atorvastatin Related Compound A RS, USP Atorvastatin Atorvastatin 3-deox-
Related Compound B RS, USP Atorvastatin Related yhept-2-enoic acide 1.45 1.0 0.10
Compound H RS, and USP Atorvastatin Related Com-
.

Atorvastatin related
pound I RS in Diluent compound Hf 1.90 1.0 0.15
Sample solution: 0.5 mg/mL of Atorvastatin Calcium in
.

Atorvastatin epoxy
Diluent. Use sonication to dissolve. [NOTE—The solution tetrahydrofuran
is stable for 3 h at room temperature and for 24 h analogg 2.00 0.71 0.15
when stored at 2°–8°, protected from light.] .

Chromatographic system Atorvastatin ethyl

(See Chromatography 〈621〉, System Suitability.) esterh . 2.08 1.0 0.15
Mode: LC Atorvastatin related
Detector: UV 254 nm compound Di . 2.18 1.3 0.15
Column: 4.6-mm × 25-cm; 4-µm packing L11 Atorvastatin related
Temperatures compound Ij . 2.75 1.0 0.15
Column: 40° Any other individual
Autosampler: 4° —
impurity 1.0 0.10
Flow rate: 1.1 mL/min Total impuritiesk — — 1.0
Injection volume: 15 µL
.

a (3R,5R)-7-{(3R,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenyl-
System suitability .

carbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanamido}-3,5-dihydrox-
Sample: Peak identification solution yheptanoic acid.
Suitability requirements b Desfluoro impurity.
.

Peak-to-valley ratio: NLT 2 between the peaks for c 3S,5R Isomer.

USP Monographs

atorvastatin related compound B and atorvastatin d Difluoro impurity.

.

Analysis e (S,E)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-
.

Sample: Sample solution pyrrol-1-yl]-5-hydroxyhept-2-enoic acid.

Calculate the percentage of each impurity in the por- f Lactone impurity.
.

tion of Atorvastatin Calcium taken: g 4-(4-Fluorophenyl)-2,4-dihydroxy-2-isopropyl-N,5-diphenyl-3,6-dioxabi-

.

cyclo[3.1.0]hexane-1-carboxamide.
h (3R,5R)-Ethyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenyl-
Result = (rU/rT) × (1/F) × 100 .

carbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate.
i Epoxide impurity.
rU = peak response of the impurity from the .

j Acetonide impurity.
Sample solution .

k This total does not include atorvastatin related compound E, as deter-

rT = sum of all the peak responses, each divided by .

mined in the Enantiomeric Purity test.

the corresponding value of the relative
response factor from Table 5
F = relative response factor for the impurity (see
Table 5)
Acceptance criteria: See Table 5. Disregard any peak
eluting before 2 min and any peak observed in the
blank; the reporting level for impurities is 0.05%.
• ENANTIOMERIC PURITY
Mobile phase: Hexane, dehydrated alcohol, and tri-
fluoroacetic acid (940:60:1)
System suitability stock solution: 5 mg/mL of USP
Atorvastatin Calcium RS and 37.5 µg/mL of USP Atorva-
statin Related Compound E RS in methanol. [NOTE—
Atorvastatin related compound E is the 3S,5S enanti-
omer of atorvastatin.]
System suitability solution: Transfer 2.0 mL of the Sys-
tem suitability stock solution to a 10-mL volumetric flask,
add 2.0 mL of dehydrated alcohol, and dilute with hex-
ane to volume.
Sample solution: Transfer 10 mg of Atorvastatin Cal-
cium to a 10-mL volumetric flask, dissolve in 2.0 mL of
methanol, add 2.0 mL of dehydrated alcohol, and dilute
with hexane to volume.

Official from May 1, 2018

Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
Accessed from 59.99.44.69 by universetx608 on Sat May 05 02:33:19 EDT 2018
USP 41
Chromatographic system
(See Chromatography 〈621〉, System Suitability.)
Mode: LC
Detector: UV 244 nm
Column: 4.6-mm × 25-cm; packing L51
Flow rate: 1.0 mL/min
Injection volume: 20 µL
System suitability
Sample: System suitability solution
[NOTE—The elution order of the peaks is atorvastatin
related compound E followed by atorvastatin.]
Resolution: NLT 2.0 between the peaks for atorvasta-
tin related compound E and atorvastatin
Analysis
Sample: Sample solution
Calculate the percentage of atorvastatin related com-
pound E in the portion of Atorvastatin Calcium taken:
Result = (rU/rT) × 100
rU = peak response for atorvastatin related
compound E
rT = sum of the peak responses for atorvastatin
related compound E and atorvastatin
Acceptance criteria: NMT 0.3% of atorvastatin related
compound E
SPECIFIC TESTS
• WATER DETERMINATION, Method Ia 〈921〉: 3.5%–5.5% for
the trihydrate form. If labeled as amorphous or as semi-
crystalline, NMT 6.0%. If labeled as a propylene glycol
solvate, NMT 1.0%.
ADDITIONAL REQUIREMENTS
• PACKAGING AND STORAGE: Preserve the trihydrate form in
well-closed containers, and store at room temperature. If
labeled as amorphous or semicrystalline or as a propylene
glycol solvate, store as per labeling instructions. Possible
packaging and storage conditions could include the fol-
lowing: Preserve in well-closed containers protected from
light and moisture, or in tight containers; store at room
temperature, at controlled room temperature, or at
2°–8°; store under nitrogen atmosphere or packed with
an oxygen absorber; and store under nitrogen atmos-
phere, packed with silica gel and an oxygen absorber.
• LABELING: Where it is an amorphous form, the label so
indicates. Where it is a semicrystalline form, the label so
indicates. Where it is a propylene glycol solvate form, the
label so indicates. If a test for Organic Impurities other
than Procedure 1 is used, the labeling states the test with
which the article complies. Label it to indicate the name
and quantity of any added antioxidant.
• USP REFERENCE STANDARDS 〈11〉
USP Atorvastatin Calcium RS
USP Atorvastatin Related Compound A RS
Desfluoro impurity, or (3R,5R)-7-[3-(phenylcarbamoyl)-
2-isopropyl-4,5-diphenyl-1H-pyrrol-1-yl]-3,5-dihydrox-
yheptanoic acid, calcium salt.
C66H70CaN4O10 1119.38
USP Atorvastatin Related Compound B RS
3S,5R Isomer, or (3S,5R)-7-[3-(phenylcarbamoyl)-
5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-
3,5-dihydroxyheptanoic acid, calcium salt.
C66H68CaF2N4O10 1155.34
USP Atorvastatin Related Compound C RS
Difluoro impurity, or (3R,5R)-7-[3-(phenylcarbamoyl)-
4,5-bis(4-fluorophenyl)-2-isopropyl-1H-pyrrol-1-yl]-3,5-
dihydroxyheptanoic acid, calcium salt.
C66H66F4N4O10 1191.34
USP Atorvastatin Related Compound D RS
Epoxide impurity, or 3-(4-fluorobenzoyl)-2-isobutyryl-
3-phenyl-oxirane-2-carboxylic acid phenylamide.
Official from May 1, 2018
Copyright (c) 2018 The United States Pharmacopeial Convention. All rights reserved.
Official Monographs / Atorvastatin 395
C26H22FNO4 431.46
USP Atorvastatin Related Compound E RS
3S,5S Enantiomer, or (3S,5S)-7-[3-(phenylcarbamoyl)-
5-(4-fluorophenyl)-2-isopropyl-4-phenyl-1H-pyrrol-1-yl]-
3,5-dihydroxyheptanoic acid, calcium salt.
C66H68CaF2N4O10 1155.34
USP Atorvastatin Related Compound H RS (lactone
impurity)
5-(4-Fluorophenyl)-1-{2-[(2R,4R)-4-hydroxy-6-oxote-
trahydro-2H-pyran-2-yl]ethyl}-2-isopropyl-N,4-diphenyl-
1H-pyrrole-3-carboxamide.
C33H33FN2O4 540.62
USP Atorvastatin Related Compound I RS (acetonide
impurity)
tert-Butyl 2-((4R,6R)-6-{2-[2-(4-fluorophenyl)-5-isopro-
pyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]ethyl}-
2,2-dimethyl-1,3-dioxan-4-yl)acetate.
C40H47FN2O5 654.81
Add the following:
.
▲ Atorvastatin Calcium Tablets
.
DEFINITION
Atorvastatin Calcium Tablets contain an amount of atorvas-
tatin calcium [(C33H34FN2O5)2Ca], equivalent to NLT
94.5% and NMT 105.0% of the labeled amount of
atorvastatin.
IDENTIFICATION
• A. The UV absorption spectrum of the major peak of the
Sample solution corresponds to that of the Standard solu-
tion, as obtained in the Assay.
USP Monographs
• B. The retention time of the major peak of the Sample
solution corresponds to that of the Standard solution, as
obtained in the Assay.
ASSAY
• PROCEDURE
Buffer: 0.05 M ammonium citrate buffer pH 4.0 pre-
pared as follows. Dissolve 9.62 g of anhydrous citric
acid in 950 mL of water, adjust with ammonium hy-
droxide to a pH of 4.0, and dilute with water to
1000 mL.
Mobile phase: Acetonitrile, stabilizer-free tetrahydro-
furan, and Buffer (27:20:53)
Solution A: Dissolve 9.62 g of anhydrous citric acid in
900 mL of water, adjust with ammonium hydroxide to
a pH of 7.4, and dilute with water to 1000 mL.
Diluent: Acetonitrile and Solution A (1:1)
System suitability solution: 0.1 mg/mL of USP Atorvas-
tatin Calcium RS and 0.01 mg/mL of USP Atorvastatin
Related Compound H RS in Diluent. Shake mechanically
for 30 min or until dissolved.
Standard solution: 0.1 mg/mL of USP Atorvastatin Cal-
cium RS in Diluent. Shake mechanically for 15 min or
until dissolved.
Sample stock solution: Prepare a known nominal con-
centration of atorvastatin by transferring NLT 10 Tablets
to an appropriate volumetric flask. Add Diluent to about
50% of the final volume of the flask, and shake the
mixture mechanically for 15 min or until dissolved. Di-
lute with Diluent to volume. Centrifuge or pass through
a suitable filter of 0.45-µm pore size.
Sample solution: Nominally equivalent to 0.1 mg/mL
of atorvastatin in Diluent from the Sample stock solution