Haloperidol Decanoate

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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C₃₁H₄₁CIFNO₃ 530.12 (USP 1-May-2021)

Decanoic acid, 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidinyl ester;

4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate (USP 1-May-2021) CAS RN^®: 74050-97-8; UNII: AC20PJ4101.

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1 DEFINITION

Haloperidol Decanoate contains NLT 97.0% and NMT 103.0% of haloperidol decanoate (USP 1-May-2021) (C₃₁H₄₁CIFNO₃), calculated on the dried basis.

2 IDENTIFICATION

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A. SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197A or (USP 1-May-2021) 197M

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B. The retention time of the major peak (USP 1-May-2021) of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

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C. IDENTIFICATION TESTS-GENERAL (191), Chemical Identification Tests, Chloride

Sample solution: Mix 0.1 g of the sample with 0.5 g of anhydrous sodium carbonate in a porcelain crucible. Heat over open flame for 10 min. Allow to cool. Dissolve the residue in 5 mL of dilute nitric acid, and filter. Dilute 1 mL of the filtrate with 1 mL of water.

Acceptance criteria: Meets the requirements of test A (USP 1-May-2021)

3 ASSAY

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3.1 PROCEDURE

Solution A: 27 g/L of tetrabutylammonium hydrogen sulfate in water

Solution B: Acetonitrile

Mobile phase: See Table 1.

Table 1

Standard solution: 0.2 mg/mL of USP Haloperidol Decanoate RS in methanol

Sample solution: 0.2 mg/mL of Haloperidol Decanoate in methanol

3.2 Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4-mm × 10-cm; 3-µm packing L1

Flow rate: 1.5 mL/min

Injection volume: (USP 1-May-2021) 10 µL

3.3 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.5

Relative standard deviation: NMT 0.73% (USP 1-May-2021)

3.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of haloperidol decanoate (C₃₁H₄₁CIFNO₃) in the portion of Haloperidol Decanoate (USP 1-May-2021) taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Acceptance criteria: 97.0%-103.0 % on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

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4.2 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, and Chromatographic system: (USP 1-May-2021) Proceed as directed in the Assay.

System suitability solution: 0.05 mg/mL each of USP Haloperidol Decanoate RS and USP Bromperidol Decanoate RS in methanol

Standard stock solution: 0.2 mg/mL of USP Haloperidol Decanoate RS in methanol

Standard solution: 0.05 mg/mL of USP Haloperidol Decanoate RS in methanol, from Standard stock solution

Sensitivity solution: 0.005 mg/mL of USP Haloperidol Decanoate RS in methanol, from Standard stock solution (USP 1-May-2021)

Sample solution: 10 mg/mL of Haloperidol Decanoate in methanol

(USP 1-May-2021)

System suitability

Samples: System suitability solution and Sensitivity solution

[NOTE-The relative retention time for bromperidol decanoate is 1.05. See Table 2 for the other relative retention times.] (USP 1-MAY-2021)

Suitability requirements

Resolution: NLT 1.5 between haloperidol decanoate and bromperidol decanoate, System suitability solution

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2021)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each impurity in the portion of Haloperidol Decanoate taken:

Result = (r_U/r_S) x (C_S/C_U) x 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of haloperidol decanoate from the Standard solution

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

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

Acceptance criteria: See Table 2. The reporting threshold is 0.05%. (USP 1-May-2021)

Table 2

^a 4-[4-(4-Chlorophenyl)-4-hydroxypiperidino]-4 (USP 1-May-2021) -fluorobutyrophenone.

^b 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl octanoate.

^c 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl nonanoate.

^d 1-[4-(4-Fluorophenyl)-4-oxobutyl]-4-phenylpiperidin-4-yl decanoate.

^e 4-(4-Chlorophenyl)-1-[4-(2-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate.

^f 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl undecanoate.

^g 4-(4-Chlorophenyl)-1-[4-(3-ethyl-4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate.

^h 4-(4-Chlorophenyl)-1-(4-{4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]phenyl}-4-oxobutyl)piperidin-4-yl decanoate.

ⁱ 4-(4-Chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl dodecanoate.

^j 4-(3'-Chlorobiphenyl-4-yl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate.

^k 4-(4'-Chlorobiphenyl-4-yl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate.

5 SPECIFIC TESTS

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LOSS ON DRYING (731)

Analysis: Dry under vacuum over phosphorous pentoxide at 30° to constant weight.

Acceptance criteria: NMT 0.5% (USP 1-May-2021)

6 ADDITIONAL REQUIREMENTS

6.1 PACKAGING AND STORAGE

Preserve in light-resistant, tight containers. Store at room temperature.

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6.2 USP REFERENCE STANDARDS (11)

USP Bromperidol Decanoate RS

4-(4-Bromophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate;

Also known as (USP 1-May-2021) Decanoic acid, 4-(4-bromophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]-4-piperidinyl ester.

C₃₁H₄₁BrFNO₃ 574.58(USP 1-May-2021)

USP Haloperidol Decanoate RS