Nicotine Polacrilex

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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[(C₄H₆O₂)_x(C₁₀H₁₀)_y] (C₁₀H₁₄N₂)

2-Propenoic acid, 2-methyl-, polymer with diethenylbenzene, complex with (S)-3-(1-methyl-2-pyrrolidinyl)pyridine;

Methacrylic acid polymer with divinylbenzene, complex with nicotine CAS RN^®: 96055-45-7.

1 DEFINITION

Nicotine Polacrilex is a weak carboxylic cation-exchange resin prepared from methacrylic acid and divinylbenzene, in complex with nicotine. It may contain glycerin. Glycerin-free Nicotine Polacrilex contains NLT 95.0% and NMT 115.0% of the labeled amount of nicotine (C₁₀H₁₄N₂). calculated on the dried basis. Glycerin-containing Nicotine Polacrilex contains NLT 95.0% and NMT 115.0% of the labeled amount of nicotine (C₁₀H₁₄N₂), calculated on the anhydrous basis.

[NOTE-Nicotine Polacrilex is also known as Nicotine Resinate.]

2 IDENTIFICATION

Change to read:

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

Sample: Transfer an amount of Nicotine Polacrilex equivalent to 100 mg of nicotine to a 100-mL glass-stoppered tube. Add 20 mL of 1 M ammonium hydroxide, 5 mL of 10 M sodium hydroxide, and 20 mL of n-hexane. Shake for 5 min, and allow the phases to separate. Transfer the upper hexane phase to an evaporating dish, and evaporate on a steam bath.

Standard: Use USP Nicotine Bitartrate Dihydrate RS, and prepare as directed for the Sample.

Acceptance criteria: Meets the requirements

Change to read:

B.^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy (for Polacrilex): 197K or 197A _{▲(CN 1-May-2020)}

Standard: Transfer a portion of USP Polacrilex Resin RS, equivalent to the amount of Nicotine Polacrilex used to prepare the Sample solution in the Assay, to a glass-stoppered tube. Add 10 mL of 1 M ammonium hydroxide, shake for 10 min, and then centrifuge. Decant the ammonia solution from the residue, and wash the residue by shaking it with three 10-mL volumes of water, decanting the water phase after each shaking. Wash with 10 mL of 0.1 N hydrochloric acid, decant the liquid, and dry the residue at 105°.

Sample: Use the residue obtained from the Sample solution in the Assay. Decant the ammonia solution remaining from the residue, and wash the residue by shaking it with three 10-mL volumes of water, decanting the water phase after each shaking. Wash with 10 mL of 0.1 N hydrochloric acid, decant the liquid, and dry the residue at 105°.

Acceptance criteria: Meets the requirements

C. 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

Solution A: Add 25 mL of 1 M acetic acid to 900 ml of water, and then add 6 mL of ammonium hydroxide. Adjust with either 2 M acetic acid or 2 M ammonium hydroxide to a pH of 10.0, and dilute with water to 1000 mL.

Solution B: Acetonitrile

Mobile phase: See Table 1. [NOTE-Re-equilibration time may be adjusted, if necessary.]

Table 1

System suitability solution: 1.5 mg/mL of USP Nicotine Bitartrate Dihydrate RS and 6 µg/mL of USP Nicotine Related Compound G RS in water

Standard solution: 1.8 mg/mL of USP Nicotine Bitartrate Dihydrate RS in water

Sample solution: Nominally 0.6 mg/mL of nicotine prepared as follows. Transfer an amount of Nicotine Polacrilex equivalent to 30 mg of nicotine to a glass-stoppered tube. Add 10.0 mL of 1 M ammonium hydroxide, shake vigorously for 10 min, and then centrifuge. Transfer 5.0 mL of the clear solution to a 25-mL volumetric flask, add 5 mL of 1 M acetic acid, and dilute with water to volume. Retain the residue from centrifugation for use in Identification B.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 2.5 between nicotine and nicotine related compound G, System suitability solution

Tailing factor: NMT 2.0 for nicotine, 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 nicotine (C₁₀H₁₄N₂) in the portion of Nicotine Polacrilex taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of nicotine from the Sample solution

r_S = peak response of nicotine from the Standard solution

C_S = concentration of USP Nicotine Bitartrate Dihydrate RS on the anhydrous basis in the Standard solution (mg/mL)

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

M_r1 = molecular weight of nicotine, 162.23

M_r2 = molecular weight of anhydrous nicotine bitartrate, 462.41

Acceptance criteria:

Glycerin free: 95.0%-115.0% on the dried basis

Glycerin containing: 95.0%-115.0% on the anhydrous basis

4 PERFORMANCE TESTS

NICOTINE RELEASE

Solution A: 9 mg/mL of sodium chloride in water

Sample stock solution: Transfer an amount of Nicotine Polacrilex equivalent to 4 mg of nicotine to a glass-stoppered tube, add 10.0 mL of Solution A that has been warmed to 37°, and shake by mechanical means for 10 min. Immediately pass the liquid through a dry filter paper, discarding the first milliliter of the filtrate.

Sample solution: Transfer 1.0 mL of the Sample stock solution to a 25-mL volumetric flask, and dilute with 0.1. N hydrochloric acid to volume.

Instrumental conditions

(See Ultraviolet-Visible Spectroscopy (857),)

Mode: UV

Analytical wavelengths: 236, 259, and 282 nm

Blank: 1.0 mL of Solution A diluted with 0.1 N hydrochloric acid to 25 mL

Analysis

Samples: Sample solution and Blank

Calculate the percentage of nicotine (C₁₀H₁₄N₂) released:

                         Result = (A₂₅₉ - 0.5A₂₃₆ - 0.5A₂₈₂) x (V/E) x (F/W) x (1/P) x 100

A₂₅₉ = absorbance of the Sample solution, corrected for the Blank absorbance, at a wavelength of 259 nm

A₂₃₆ = absorbance of the Sample solution, corrected for the Blank absorbance, at a wavelength of 236 nm

A₂₈₂ = absorbance of the Sample solution, corrected for the Blank absorbance, at a wavelength of 282 nm

V = dilution volume, 250 mL

E = specific absorbance of nicotine at a wavelength of 259 nm, 323 mL g^-1 cm^-1

F = unit conversion factor, 1000 mg/g

W = weight of Nicotine Polacrilex (mg)

P = percentage of nicotine in Nicotine Polacrilex determined in the Assay

Acceptance criteria: NLT 70% in 10 min

5 IMPURITIES

ORGANIC IMPURITIES

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

System suitability solution: 1.5 mg/mL of USP Nicotine Bitartrate Dihydrate RS and 6 µg/ml. each of USP Nicotine Related Compound A RS, USP Nicotine Related Compound B RS, USP Nicotine Related Compound C RS, USP Nicotine Related Compound D RS, USP Nicotine Related Compound E RS, USP Nicotine Related Compound FRS, and USP Nicotine Related Compound G. RS in water. [NOTE-The concentration of each related compound is in terms of the free base.]

Standard solution: 1.8 µg/mL of USP Nicotine Bitartrate Dihydrate RS in water

Sensitivity solution: 0.9 µg/mL of USP Nicotine Bitartrate Dihydrate RS in water from the Standard solution

System suitability

Samples: System suitability solution, Standard solution, and Sensitivity solution

[NOTE-See Table 2 for the relative retention times.]

Suitability requirements

Resolution: NLT 2.5 between nicotine and nicotine related compound G, System suitability solution

Tailing factor: NMT 2.0 for nicotine, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

Analysis

Samples: Sample solution and Standard solution

Calculate the percentage of each impurity in the portion of Nicotine Polacrilex taken:

                         Result = (r_U/r_S) × (C_S/C_U) × (M_r1/M_r2) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of nicotine from the Standard solution

C_S = concentration of USP Nicotine Bitartrate Dihydrate RS on the anhydrous basis in the Standard solution (mg/mL) 

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

M_r1 = molecular weight of nicotine, 162.23

M_r2 = 1 molecular weight of anhydrous nicotine bitartrate, 462.41

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

6 SPECIFIC TESTS

WATER DETERMINATION (921), Method / (for glycerin-containing Nicotine Polacrilex)

Sample solution: Transfer about 1.0 g of Nicotine Polacrilex to a 50-mL glass-stoppered test tube, and add 20.0 mL of methanol. Shake for 30 min, and allow to stand for 30 min. Use a 10-mL portion of the methanol layer for the titration.

Acceptance criteria: NMT 5.0%

LOSS ON DRYING (731), (for glycerin-free Nicotine Polacrilex)

Analysis: Dry at 105° for 2 h.

Acceptance criteria: NMT 7.0%

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers, protected from light.

LABELING: Label to indicate if the article contains glycerin.

USP REFERENCE STANDARDS (11)

USP Nicotine Bitartrate Dihydrate RS

USP Nicotine Related Compound A RS

Anatabine;

1,2,3,6-Tetrahydro-2,3'-bipyridine.

C₁₀H₁₂N₂         160.22

USP Nicotine Related Compound B. RS

3-(1-Methyl-1H-pyrrol-2-yl)pyridine; Also known as Nicotyrine.

C₁₀H₁₀N₂          158.20

USP Nicotine Related Compound. C. RS

(S)-1-Methyl-5-(pyridin-3-yl)pyrrolidin-2-one; Also known as Cotinine.

C₁₀H₁₂N₂O          176.22

USP Nicotine Related Compound D. RS

3-(4,5-Dihydro-3H-pyrrol-2-yl)pyridine fumarate; Also known as Myosamine.

C₉H₁₀N₂O · C₂H₂O₄          262.26

USP Nicotine Related Compound ERS

(1RS,2S)-1-Methyl-2-(pyridin-3-yl)pyrrolidine 1-oxide oxalate; Also known as Nicotine N-oxide.

C₁₀H₁₄N₂O · C₂H₂O₄             268.27

USP Nicotine Related Compound FRS

3-(Pyrrolidin-2-yl)pyridine; Also known as Nornicotine.

C₉H₁₂N₂         148.20

USP Nicotine Related Compound G.RS

(S)-3-(Piperidin-2-yl)pyridine; Also known as Anabasine.

C₁₀H₁₄N₂         162.23

USP Polacrilex Resin RS