Moxidectin

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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C₃₇H₅₃NO₈        639.82

(6R,25S)-5-O-Demethyl-28-deoxy-25-[(E)-1,3-dimethyl-1-butenyl]-6,28-epoxy-23-oxomilbemycin B 23-(E)-(O-methyloxime);

(2aE,4E,5'R,6R,6'S,8E, 11R,13S, 15S, 17aR,20R,20aR,20bS)-6'-[(E)-1,3-Dimethyl-1-butenyl]-5,6,6,7,10,11,14,15,17,20,20a,20b-dodecahydro-20,20b-dihydroxy-5',6,8,19-tetramethylspiro (11,15-methano-2H,13H,17H-furo [4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(0-methyloxime) CAS RN^®: 113507-06-5; UNII: NGU5H31Y09.

1 DEFINITION

Moxidectin contains NLT 92.0% and NMT 102.0% of moxidectin (C₃₇H₅₃NO₈), calculated on the anhydrous basis. It may contain a suitable antioxidant.

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{▲(CN 1-MAY-2020)}

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: Dissolve 7.7 g of ammonium acetate in 400 mL of water, and adjust with glacial acetic acid to a pH of 4.8.

Mobile phase: Acetonitrile and Buffer (60:40)

Standard solution: 1.0 mg/mL of USP Moxidectin RS in acetonitrile. Sonicate if necessary to facilitate dissolution.

Sample solution: 1.0 mg/mL of Moxidectin in acetonitrile. Sonicate if necessary to facilitate dissolution.

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 242 nm

Column: 3.9-mm x 15-cm; 4-µm packing L1

Column temperature: 50°

Flow rate: 2.5 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

Suitability requirements

Relative standard deviation: NMT 1%, for 4 replicate injections

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of moxidectin (C₃₇H₅₃NO₈) in the portion of Moxidectin taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution 

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

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

Acceptance criteria: 92.0%-102.0% on the anhydrous basis

4 IMPURITIES

RESIDUE ON IGNITION (281): NMT 0.2%

Delete the following:

HEAVY METALS, Method II (231): NMT 20 ppm _{▲(Official 1-Jan-2018)}

4.1 ORGANIC IMPURITIES: EARLY-ELUTING IMPURITIES

Buffer, Mobile phase, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: 1.0 mg/mL of USP Moxidectin System Suitability Mixture RS in acetonitrile. Sonicate if necessary to facilitate dissolution.

Standard solution: 0.01 mg/mL of Moxidectin in acetonitrile from the Sample solution

System suitability

Sample: System suitability solution

Suitability requirements

Peak-to-valley ratio: NLT 3.0 between moxidectin 17a-epimer and moxidectin

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each early-eluting impurity in the portion of Moxidectin taken:

                         Result = (r_U/r_S) x F x D x 100

r_U = peak response of each early-eluting impurity from the Sample solution

r_S = peak response of moxidectin from the Standard solution

F = Assay value expressed as a decimal

D= dilution factor used to prepare the Standard solution, 0.01 

Acceptance criteria: See Table 1.

The reporting level for impurities is 0.1%. Disregard the peak due to the stabilizer (identify this peak, where applicable, by injecting a suitable reference solution).

Table 1

^a (2aE,4E,5'R,6R, 6'S,8E, 11R,13S, 15S, 17aR, 20R,20aR,20bS)-6'-[(E)-But-2-en-2-yl]-5',6,6',7,10,11,14,15,17a,20,20a, 20b-dodecahydro-20,20b-dihydroxy-5',6,8,19-tetramethylspiro [11,15-methano-2H, 13H,17H-furo [4,3,2-pq][2,6] benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^b (2aE,4E,5'R,6R,6'S,8E, 11R,13S, 15S, 17aR,20R,20aR,20bS)-5',6,6',7,10,11,14,15,17a,20,20a, 20b-Dodecahydro-20,20b-dihydroxy-6'-[(E)-4-methylpent-2-en-2-yl]-6,8,19-trimethylspiro [11,15-methano-2H, 13H,17H-furo [4,3,2-pq][2,6] benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^c (2aE,4E,5'R,6R,6'S,8E, 11R,13S, 15S, 17aR,20R,20aR,20bS)-5',6,6,7,10,11,14,15,17,20,20a, 20b-Dodecahydro-20,20b-dihydroxy-5,6,8,19-tetramethyl-6'-[(E)-pent-2-en-2-yl]spiro [11,15-methano-2H, 13H,17H-furo [4,3,2-pq][2,6] benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^d (2aE,4E,5'R,6R,6'S,8E,11R,135, 155, 17aS,20R,20aR,20bS)-5',6,6',7,10,11,14,15,17a,20,20a, 20b-Dodecahydro-20,20b-dihydroxy-6'-[(E)-4-methylpent-2-en-2-yl)-5',6,8,19-tetramethylspiro (11,15-methano-2H, 13H,17H-furo[4,3,2-pq][2,6] benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^e (2aE,4E,5'R,6R,6'S,8E, 11R,13S, 15S,19S,20R,20aR,20bS)-5',6,6',7,10,11,14,15,19,20,20a,20b-Dodecahydro-20,20b-dihydroxy-6'-[(E)-4-methylpent-2-en-2-yl]-5,6,8,19-tetramethylspiro [11,15-methano-2H,13H,17H-furo [4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'-[2]ругап]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^f Mixture of five possible isomers, where one methyl group in the analyte is replaced with an ethyl group.

^g If present, moxidectin 19-S-17a-ene and the moxidectin ethyl isomers may not be completely resolved by the method. These peaks are integrated together to determine conformance.

^h (2'R,35,5'S,6'S,7R,9E, 12R, 13E,15E, 16aS, 18S,20aR)-16a, 18-Dihydroxy-5',10,12,16,19-pentamethyl-6'-[(E)-4-methylpent-2-en-2-yl]-3,4, 5,6,7,8,11,12,16,17,18,20a-dodecahydro-1H-spiro[3,7-methanobenzo[g][1,5]dioxacyclooctadecin-5,2'-[2H]pyran]-14'-dione (E)-(O-methyloxime).

4.2 ORGANIC IMPURITIES: LATE-ELUTING IMPURITIES

Buffer: Dissolve 3.8 g of ammonium acetate in 250 mL of water, and adjust with glacial acetic acid to a pH of 4.2.

Mobile phase: Acetonitrile and Buffer (75:25)

System suitability solution: 3.0 mg/mL of USP Moxidectin System Suitability Mixture RS in acetonitrile. Sonicate if necessary to facilitate dissolution.

Sample solution: 3.0 mg/mL of Moxidectin in acetonitrile. Sonicate if necessary to facilitate dissolution.

Standard solution: 0.03 mg/mL of Moxidectin in acetonitrile from the Sample solution

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 242 nm

Column: 3.9-mm x 15-cm; 4-um packing L1

Column temperature: 35°

Flow rate: 2 mL/min

Injection volume: 10 µL

Run time: NLT 10 times the retention time of moxidectin

System suitability

Sample: System suitability solution

Suitability requirements

Resolution: NLT 1.0 between moxidectin deoxydiene/methylthiomethoxymoxidectin and 20b-methylthiomoxidectin

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each late-eluting impurity in the portion of Moxidectin taken:

                         Result = (r_U/r_S) x Fx D x 100

r_U = peak response of each late-eluting impurity from the Sample solution 

r_S = peak response of moxidectin from the Standard solution 

F = Assay value expressed as a decimal

D = dilution factor used to prepare the Standard solution, 0.01

Acceptance criteria: See Table 2.

The reporting level for impurities is 0.1%. Disregard the peak due to the stabilizer (identify this peak, where applicable, by injecting a suitable reference solution).

Table 2

^a (2aE,4E,5'R,6R,6'S,8E, 11R,13S, 15S,20aR,20bS)-5',6,6',7,10,11,14,15,20a,20b-Decahydro-20b-hydroxy-6'-[(E)-4-methylpent-2-en-2-yl]-5',6,8,19-tetramethylspiro [11,15-methano-2H, 13H,17H-furo [4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^b (2aE,4E,4'S,5 R,6R, 6'S,8E, 11R,13S, 15S,17aR,20R,20aR,20bS)- 3',4',5',6,6',7,10,11,14,15,17,20,20a,20b-Tetradecahydro-20,20b-dihydroxy-6'-[(E)-4-methylpent-2-en-2-yl]-4'-methylthiomethoxy-5',6,8,19-tetramethylspiro [11,15-methano-2H, 13H,17H-furo[4,3,2-pq][ 2,6] benzodioxacyclooctadecin-13,2'-[2H]pyran]-17-one.

^c If present, impurities moxidectin deoxydiene and 4-methylthiomethoxymoxidectin may not be completely resolved by the method. These peaks are integrated together to determine conformance.

^d (2aE,4E,5'R,6R,6'S,8E, 11R,13S, 15S, 17aR,20R,20aR,20bS)-5',6,6',7,10,11,14,15,17,20,20a,20b-Dodecahydro-20-hydroxy-6'-[(E)-4-methylpent-2-en-2-yl]-20b-methylthiomethoxy-5',6,8,19-tetramethylspiro [11,15-methano-2H,13H,17H-furo[4,3,2-pq][2,6]benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

^e (2aE,4E,5'R,6R,6'S,8E, 11R,135,155,17aR,20R,20aR,20bS)-5',6,6',7,10,11,14,15,17,20,20a,20b-Dodecahydro-20b-hydroxy-6'-[(E)-4-methylpent-2-en-2-yl]-20-(4-nitrobenzoyloxy)-5',6,8,19-tetramethylspiro [11,15-methano-2H,13H,17H-furo[4,3,2-pq] [2,6] benzodioxacyclooctadecin-13,2'-[2H]pyran]-4',17(3'H)-dione 4'-(E)-(O-methyloxime).

4.3 TOTAL ORGANIC IMPURITIES

Analysis: Calculate the sum of all impurities found in the tests for Organic Impurities: Early-Eluting Impurities and Organic Impurities: Late-Eluting Impurities in the portion of Moxidectin taken.

Acceptance criteria: NMT 7.0%

5 SPECIFIC TESTS

WATER DETERMINATION (921), Method : NMT 1.3%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in well-closed, light-resistant containers, and store in a refrigerator.

Change to read:

LABELING: If it is intended for use in animals, it is so labeled (RB 27-Jun-2018) Label it to state the name(s) and amount(s) of any added substance(s).

USP REFERENCE STANDARDS (11)

USP Moxidectin RS

USP Moxidectin System Suitability Mixture RS