Atorvastatin Calcium Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Atorvastatin Calcium Tablets

1 DEFINITION

Atorvastatin Calcium Tablets contain an amount of atorvastatin calcium [(C₃₃H₃₄FN₂O₅)₂Ca], equivalent to NLT 94.5% and NMT 105.0% of the labeled amount of atorvastatin.

2 IDENTIFICATION

A. The UV absorption spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 0.05 M ammonium citrate buffer pH 4.0 prepared as follows. Dissolve 9.62 g of anhydrous citric acid in 950 mL of water, adjust with ammonium hydroxide to a pH of 4.0, and dilute with water to 1000 mL.

Mobile phase: Acetonitrile, stabilizer-free tetrahydrofuran, 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 Atorvastatin 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 Calcium RS in Diluent. Shake mechanically for 15 min or until dissolved.

Sample stock solution: Prepare a known nominal concentration 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. Dilute 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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector

Assay: UV 244 nm

Identification A: Diode array; UV 200–400 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements:

Resolution: NLT 5.0 between atorvastatin and atorvastatin related compound H, System suitability solution

Tailing factor: NMT 1.5 for atorvastatin, System suitability solution

Relative standard deviation: NMT 1.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) in the portion of Tablets taken:

Result = (r₁/r₂) × (C_S/C_U) × [M × (M₁/M₂)] × 100

r₁ = peak response of atorvastatin from the Sample solution

r₂ = peak response of atorvastatin from the Standard solution

C_S= concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

C_U= nominal concentration of atorvastatin in the Sample solution (mg/mL)

M = number of moles of atorvastatin per mole of atorvastatin calcium, 2

M₁ = molecular weight of atorvastatin, 558.65

M₂ = molecular weight of atorvastatin calcium, 1155.36

Acceptance criteria: 94.5%–105.0%

4 PERFORMANCE TESTS

Dissolution 〈711〉

Test 1

Buffer: 0.05 M phosphate buffer prepared as follows. Dissolve 6.8 g of monobasic potassium phosphate in 900 mL of water. Adjust with 6 N sodium hydroxide to a pH of 6.8 and dilute with water to 1 L.

Medium: Buffer; 900 mL

Apparatus 2: 75 rpm

Time: 15 min

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 1 mg/mL of USP Atorvastatin Calcium RS in Diluent. Shake mechanically for 10 min or until dissolved.

Standard solution: (L/900) mg/mL in Medium from Standard stock solution, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable filter or centrifuge prior to analysis.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 244 nm

Cell: See Table 1 or make appropriate dilutions of the solutions with Medium to be within the validated linearity range of the suitable spectrophotometer.

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) dissolved:

(A_U/A_S) × C_S × V × D × [M × (M₁/M₂)] × (1/L) × 100

A_U= absorbance of the Sample solution

A_S= absorbance of the Standard solution

C_S = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution, if applicable

M = number of moles of atorvastatin per mole of atorvastatin calcium, 2

M₁ = molecular weight of atorvastatin, 558.65

M₂ = molecular weight of atorvastatin calcium, 1155.36

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

Test 2: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2. Dissolution Test 2 is suitable for

products labeled to contain 80 mg of atorvastatin.

Medium and Apparatus 2: Proceed as directed in Test 1.

Time: 30 min

Diluent, Standard solution, Sample solution, Instrumental conditions, and Blank: Proceed as directed in Test 1.

Tolerances: NLT 85% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Buffer: Combine 250 mL of 0.2 M monobasic potassium phosphate, 112 mL of 0.2 N sodium hydroxide, and 638 mL of water. Adjust with

either 0.02 N sodium hydroxide or phosphoric acid to a pH of 6.8.

Solution A: Acetonitrile, methanol, and 0.1% triuoroacetic acid (5:5:90)

Solution B: Acetonitrile, methanol, and 0.1% triuoroacetic acid (45:45:10)

Solution C: Dissolve 50 g of ▲polysorbate 80▲ (RB 1-Sep-2023) in 1 L of Buffer.

Mobile phase: See Table 2.

Medium: Solution C and Buffer (6:94); 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Standard stock solution: 0.96 mg/mL of USP Atorvastatin Calcium RS in methanol

Standard solution: Dilute the Standard stock solution with Medium to obtain a nal concentration of (L/900) mg/mL, where L is the label

claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 248 nm

Column: 2.1-mm × 5-cm; 2.6-µm packing L1

Column temperature: 40°

Flow rate: 0.7 mL/min

Injection volume: 2 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) dissolved:

(rᵤ / rₛ) × Cₛ × V × [M × (Mᵣ₁ / Mᵣ₂)] × (1 / L) × 100

rᵤ = peak response of atorvastatin from the Sample solution

rₛ= peak response of atorvastatin from the Standard solution

Cₛ = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M= number of moles of atorvastatin per mole of atorvastatin calcium, 2

Mᵣ₁= molecular weight of atorvastatin, 558.65

Mᵣ₂= molecular weight of atorvastatin calcium, 1155.36

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅ ) is dissolved.

Test 4: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 4.

Medium: Dissolve 6.8 g of monobasic potassium phosphate and 0.89 g of sodium hydroxide in 1 L of water. Adjust with either 1 N sodium

hydroxide or phosphoric acid to a pH of 6.8; 900 mL.

Apparatus 2: 75 rpm

Time: 15 min

Buffer: Dissolve about 6.8 g of monobasic potassium phosphate in 1000 mL of water. Adjust with 0.5 N potassium hydroxide solution to a

pH of 6.0.

Mobile phase: Acetonitrile and Buffer (55:45)

Standard stock solution: 0.225 mg/mL of atorvastatin from USP Atorvastatin Calcium RS prepared as follows. To a suitable amount of USP

Atorvastatin Calcium RS, add 5% of total volume of methanol, sonicate to dissolve, and cool. Dilute with Medium to volume.

Standard solution: Dilute the Standard stock solution with Medium to obtain a nal concentration of (L/900) mg/mL, where L is the label

claim in mg/Tablet.

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 248 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Column temperature: 30°

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅ ) dissolved:

(rᵤ / rₛ) × Cₛ × V × [M × (Mᵣ₁ / Mᵣ₂)] × (1 / L) × 100

rᵤ = peak response of atorvastatin from the Sample solution

rₛ= peak response of atorvastatin from the Standard solution

Cₛ = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M= number of moles of atorvastatin per mole of atorvastatin calcium, 2

Mᵣ₁= molecular weight of atorvastatin, 558.65

Mᵣ₂= molecular weight of atorvastatin calcium, 1155.36

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

Test 5: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 5.

Medium: Dissolve 6.8 g of monobasic potassium phosphate and 0.9 g of sodium hydroxide in 1 L of water. Adjust with either sodium

hydroxide or phosphoric acid to a pH of 6.8; 900 mL.

Apparatus 2: 75 rpm

Time: 20 min

Buffer: Dissolve 10.5 g of citric acid in 1000 mL of water. Adjust with ammonium hydroxide to a pH of 4.0.

Mobile phase: Acetonitrile, tetrahydrofuran, and Buffer (50:10:40)

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 0.925 mg/mL of USP Atorvastatin Calcium RS in Diluent. Sonicate to dissolve.

Standard solution: (L/900) mg/mL in Medium from Standard stock solution, where L is the label claim in mg/Tablet. Pass the solution

through a suitable lter of 0.45-µm pore size and discard the rst few milliliters of the ltrate.

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size and discard the rst few milliliters

of the ltrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 244 nm

Column: 4.6-mm × 15-cm; 5-µm packing L1

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 2 times the retention time of atorvastatin

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅ ) dissolved:

(rᵤ / rₛ) × Cₛ × V × [M × (Mᵣ₁ / Mᵣ₂)] × (1 / L) × 100

rᵤ = peak response of atorvastatin from the Sample solution

rₛ= peak response of atorvastatin from the Standard solution

Cₛ = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M= number of moles of atorvastatin per mole of atorvastatin calcium, 2

Mᵣ₁= molecular weight of atorvastatin, 558.65

Mᵣ₂= molecular weight of atorvastatin calcium, 1155.36

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

Test 6: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 6.

Medium: 0.05 M phosphate buffer, pH 6.8, prepared as follows. Dissolve 6.8 g of monobasic potassium phosphate and 0.89 g of sodium

hydroxide in 1 L of water. Adjust with 1 N sodium hydroxide to a pH of 6.8; 900 mL.

Apparatus 2: 100 rpm

Time: 20 min

Buffer: 1.36 g/L of monobasic potassium phosphate in water

Mobile phase: Acetonitrile and Buffer (50:50). Adjust with phosphoric acid solution to a pH of 2.8.

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 0.461 mg/mL of USP Atorvastatin Calcium RS in Diluent. Sonicate to dissolve.

Standard solution: (L/900) mg/mL in Medium from Standard stock solution, where L is the label claim in mg/Tablet

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.45-µm pore size, and discard the rst few milliliters

of the ltrate.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Detector: UV 238 nm

Column: 4.6-mm × 5-cm; 5-µm packing L1

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 0.8 mL/min

Injection volume: 20 µL

Run time: NLT 2 times the retention time of atorvastatin

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

(rᵤ / rₛ) × Cₛ × V × [M × (Mᵣ₁ / Mᵣ₂)] × (1 / L) × 100

rᵤ = peak response of atorvastatin from the Sample solution

rₛ= peak response of atorvastatin from the Standard solution

Cₛ = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M= number of moles of atorvastatin per mole of atorvastatin calcium, 2

Mᵣ₁= molecular weight of atorvastatin, 558.65

Mᵣ₂= molecular weight of atorvastatin calcium, 1155.36

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

Test 7: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 7.

Medium: 0.05 M pH 6.8 phosphate buffer (dissolve 6.8 g of monobasic potassium phosphate in 900 mL of water; adjust with 6 N sodium

hydroxide to a pH of 6.8 and dilute with water to 1 L); 900 mL

Apparatus 2: 60 rpm

Time: 30 min

Diluent: Acetonitrile and water (50:50)

Standard stock solution: 1 mg/mL of USP Atorvastatin Calcium RS in Diluent. Shake mechanically for 10 min or until dissolved.

Standard solution: (L/900) mg/mL of atorvastatin, contained in USP Atorvastatin Calcium RS, from Standard stock solution in Medium,

where L is the label claim of atorvastatin in mg/Tablet. [Note—The Standard solution may be stable for 6 h at room temperature.]

Sample solution: Pass a portion of the solution under test through a suitable lter of 0.8-µm pore size, discarding the rst 3 mL of the

ltrate. [Note—The Sample solution may be stable for 6 h at room temperature.]

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy 〈857〉.)

Mode: UV

Analytical wavelength: 244 nm

Cell

For Tablets labeled to contain 10 mg: 1 cm

For Tablets labeled to contain 20 or 40 mg: 0.5 cm

For Tablets labeled to contain 80 mg: 0.2 cm

Blank: Medium

Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

(Aᵤ / Aₛ) × Cₛ × V × [M × (Mᵣ₁ / Mᵣ₂)] × (1 / L) × 100

Aᵤ = absorbance of atorvastatin from the Sample solution

Aₛ= absorbance of atorvastatin from the Standard solution

Cₛ = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

M= number of moles of atorvastatin per mole of atorvastatin calcium, 2

Mᵣ₁= molecular weight of atorvastatin, 558.65

Mᵣ₂= molecular weight of atorvastatin calcium, 1155.36

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved _{.▲ (RB 1-Sep-2023)}

5 IMPURITIES

Organic Impurities

Rinse glassware with Diluent before preparing solutions containing atorvastatin calcium.

Buffer: 5.75 g/L of monobasic ammonium phosphate in water. Adjust with dilute acetic acid (10% v/v) or dilute ammonium hydroxide (10%

v/v) to a pH of 4.3 ± 0.05.

Solution A: Acetonitrile and stabilizer-free tetrahydrofuran (925:75)

Solution B: Solution A and Buffer (42:58)

Solution C: Methanol, Solution A, and Buffer (60:20:20)

Diluent: N,N-Dimethylformamide

System suitability solution: 60 µg/mL of USP Atorvastatin Calcium RS, 50 µg/mL of USP Atorvastatin Related Compound B RS, 10 µg/mL of

USP Atorvastatin Related Compound H RS, and 0.5 µg/mL of USP Atorvastatin Related Compound D RS in Diluent

Standard solution: 5 µg/mL of USP Atorvastatin Calcium RS in Diluent. Sonication may be necessary for complete dissolution.

Sample solution: Nominally equivalent to 1 mg/mL of atorvastatin, prepared as follows. Crush and nely powder NLT 20 Tablets. Transfer the

amount of powder, equivalent to about 50 mg of atorvastatin, to a 50-mL volumetric ask. Add 30 mL of Diluent and shake mechanically for

15 min. Dilute with Diluent to volume and pass the solution through a suitable lter of 0.45-µm pore size, discarding the rst few mL of the

ltrate.

Mobile phase: See Table 3.

For the Standard solution, the run time is only 30 min. For the System suitability solution and Sample solution, the run time is 65 min.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 244 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: See Table 3.

Injection volume: 20 µL

System suitability

Sample: System suitability solution

[Note—The relative retention times of all peaks eluting before atorvastatin related compound H as given in Table 4 are calculated with

respect to the atorvastatin peak. The relative retention times for all peaks eluting after atorvastatin related compound H are calculated with

respect to atorvastatin related compound H.]

Suitability requirements

Resolution: NLT 1.4 between atorvastatin related compound B and atorvastatin

Tailing factor: NMT 1.5 for the atorvastatin peak

Relative standard deviation: NMT 5% for the atorvastatin peak

Signal-to-noise ratio: NLT 10 for atorvastatin related compound D

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Tablets taken:

Tolerances: NLT 80% (Q) of the labeled amount of atorvastatin (C₃₃H₃₅FN₂O₅) is dissolved.

Result = (rᵤ / rₛ) × (Cₛ / Cᵤ) × [M × (Mᵣ₁ / Mᵣ₂)] × (1 / F) × 100

rᵤ = peak response of atorvastatin from the Sample solution

rₛ= peak response of atorvastatin from the Standard solution

Cₛ = concentration of USP Atorvastatin Calcium RS in the Standard solution (mg/mL)

Cᵤ= nominal concentration of atorvastatin in the Sample solution (mg/mL)

M= number of moles of atorvastatin per mole of atorvastatin calcium, 2

Mᵣ₁= molecular weight of atorvastatin, 558.65

Mᵣ₂= molecular weight of atorvastatin calcium, 1155.36

F = relative response factor (see Table 4)

Acceptance criteria: See Table 4.

a: (3R,5R)-7-{(3R,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanamido}-3,5-dihydroxyheptanoic acid.

b: Process impurity included in the table for identification only. Process impurities are controlled in the drug substance, and are not to be reported or included in the total impurities for the drug product.

c: (3R,5R)-7-[2-Isopropyl-4,5-diphenyl-3-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid.

d: (3R,5R)-7-[5-(4-Fluorophenyl)-3-isopropyl-2-oxo-4-phenyl-3-(phenylcarbamoyl)-2,3-dihydro-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid.

e: (3S,5R)-7-[2-(4-Fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid.

f: (3R,5R)-7-[2,3-Bis(4-fluorophenyl)-5-isopropyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoic acid.

g: 5-(4-Fluorophenyl)-1-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3-isopropyl-2-oxo-N,4-diphenyl-2,3-dihydro-1H-pyrrole-3-carboxamide.

h: 5-(4-Fluorophenyl)-1-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide.

i: 4-{6-(4-Fluorophenyl)-7,8-epoxy-6-hydroxy-8a-isopropyl-7-phenyl-8-(phenylcarbamoyl)hexahydro-2H-pyrrolo[2,1-b][1,3]oxazin-2-yl}-3-hydroxybutanoic acid.

j: (3R,5R)-Methyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate.

k: (3R)-4-(1b-(4-Fluorophenyl)-7-hydroxy-7-isopropyl-1a-phenyl-7a-(phenylcarbamoyl)hexahydro-1aH-oxireno[2′,3′:3,4]pyrrolo[2,1-b][1,3]oxazin-3-yl)-3-hydroxybutanoic acid.

l: 4-(4-Fluorophenyl)-2,4-dihydroxy-2-isopropyl-N,5-diphenyl-3,6-dioxabicyclo[3.1.0]hexane-1-carboxamide.

m: Atorvastatin related compound D can undergo transformation equilibrium to the atorvastatin epoxy THF analog. The equilibrium can be shifted under slightly acidic conditions and therefore some products could have a combined specification reported under atorvastatin related compound D.

n: 3-(4-Fluorobenzoyl)-2-isobutyryl-N,3-diphenyloxirane-2-carboxamide.

o: (3R,5R)-tert-Butyl 7-(2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl)-3,5-dihydroxyheptanoate.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, and store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Atorvastatin Calcium RS

USP Atorvastatin Related Compound B RS

Calcium (3S,5R)-7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4-(phenylcarbamoyl)-1H-pyrrol-1-yl]-3,5-dihydroxyheptanoate (1:2). C₆₆H₆₈CaF₂N₄O₁₀ 1155.36

USP Atorvastatin Related Compound D RS

3-(4-Fluorobenzoyl)-2-isobutyryl-N,3-diphenyloxirane-2-carboxamide. C₂₆H₂₂FNO₄ 431.46

USP Atorvastatin Related Compound H RS

5-(4-Fluorophenyl)-1-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-2-isopropyl-N,4-diphenyl-1H-pyrrole-3-carboxamide. C₃₃H₃₄FN₂O₅ 540.64