What Is Triprolidine?

Triprolidine is a white or off-white crystalline powder; Chinese alias: 2-[(E) -1- (4-methylphenyl) -3- (1-pyrrolidinyl) -1-propenyl] Pyridine, molecular formula is C19H22N2, density: 1.061 g / cm3, melting point: 126-130 ° C. Odorless, bitter, easily soluble in water, methanol, ethanol or chloroform.

Chinese name: Triprolidine
Foreign name: triprolidine

CAS number: 486-12-4
Molecular formula: C19H22N2
Molecular weight: 278.39100

Introduction to triprolidine compounds

Triprolidine Basic Information

Chinese name: triprolidine

Chinese alias: 2-[(E) -1- (4-methylphenyl) -3- (1-pyrrolidinyl) -1-propenyl] pyridine; Triprolidine;

English name: triprolidine

English alias: (e) -pyridin; Triprolidin; (E) -1- (2-pyridyl) -3-pyrrolidin-1-yl-1-p-tolylpropene; trans-1- (2-Pyridyl) -3-pyrrolidino -1-p-tolylprop-1-ene;

CAS number: 486-12-4

Molecular formula: C ₁₉ H ₂₂ N ₂

Structural formula:

Molecular weight: 278.39100

Exact mass: 278.17800

PSA: 16.13000

LogP: 3.85540 ^[1]

Triprolidine physical and chemical properties

Appearance and properties: crystal

Density: 1.061 g / cm3

Melting point: 126-130 ° C

Boiling point: 435.4ºC at 760 mmHg

Flash point: 217.1ºC

Vapor pressure: 6.16E-09mmHg at 25 ° C ^[1]

Triprolidine Safety Information

Safety instructions: S36 / 37 ^[1]

Triprolidine Pharmacopoeia Standard

The main active ingredients of triprolidine

This product is (E) -2- [1- (4-Tolyl) -3- (1-pyrrolidinyl) -1-propenyl] pyridine hydrochloride monohydrate. Calculated as anhydrous, the content of C19H22N2 · HCl should not be less than 98.5%. ^[2]

Triprolidine traits

This product is white or off-white crystalline powder; odorless and bitter. This product is soluble in water, methanol, ethanol or chloroform.

Triprolidine identification

(1) In the chromatogram recorded under the relevant substance inspection item, the retention time of the main peak of the test solution should be consistent with the retention time of the triprolidine hydrochloride reference peak in the system suitability solution.

(2) Take an appropriate amount of this product, dissolve and dilute it with a 0.1mol / L hydrochloric acid solution to make a solution containing about 20g per 1ml, and measure it according to the UV-visible spectrophotometry (Chinese Pharmacopoeia 2015 Edition Four General Rules 0401). Maximum absorption at wavelength.

(3) The infrared absorption spectrum of this product should be the same as that of the reference substance (Chinese Pharmacopoeia 2015 Edition Four General Rules 0402).

(4) Identification of chlorides in aqueous solution of this product (Chinese Pharmacopoeia 2015 Edition Four General Rules 0301). ^[2]

Triprolidine examination

1 Clarity and color of solution

Take this product and use water to make a solution containing about 0.10g per 1ml. The solution should be clear and colorless; if it is turbid, compare it with No. 1 turbidity standard solution (Chinese Pharmacopoeia 2015 Edition Four General Rules 0902 first method). If it is colored, it must not be deeper compared with the yellow or yellow-green standard colorimetric liquid No. 2 (the first method of General Regulation 0901 of the Fourth Edition of the Chinese Pharmacopoeia 2015 Edition). ^[2]

2 related substances

Protect from light. Take an appropriate amount of this product, accurately weigh, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 1mg per 1ml, as the test solution; take 1ml for precise measurement, place it in a 100ml measuring flask, and dilute to the mark with mobile phase , Shake well, as a control solution; take an appropriate amount of triprolidine hydrochloride cis isomer reference, accurately weigh, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 20g per 1ml, as an impurity reference Solution. Take an appropriate amount of the triprolidine hydrochloride reference and the triprolidine hydrochloride cis isomer reference, add the mobile phase to dissolve and dilute, and make about 1 mg of triprolidine hydrochloride and triprolidine hydrochloride per 1ml. A 20 g mixed solution of formula isomers is used as a system suitability solution. Take an appropriate amount of the control solution and the impurity reference solution, place them in the same volume bottle, and dilute with mobile phase to make each 1ml containing triprolidine hydrochloride and kojitril hydrochloride. A solution of about 1 g of each of the cis isomers of Pridine was used as a sensitivity solution.

According to high performance liquid chromatography (Chinese Pharmacopoeia 2015 Edition Four General Rules 0512), using octadecylsilane bonded silica as a filler, methanol-ammonium acetate solution (take 600ml 0.4% ammonium acetate solution, add 2ml triethylamine, Adjust the pH value to 7.0 with glacial acetic acid (65:35) as the mobile phase, and the detection wavelength is 260nm. Take 10µl of the system suitability solution and inject it into the liquid chromatograph. Record the chromatogram. The resolution of the cis isomer peak of triprolidine hydrochloride and the peak of triprolidine hydrochloride should meet the requirements. Take 10µl of the sensitivity solution and inject it into the liquid phase. For a chromatograph, the signal-to-noise ratio of both the triprolidine hydrochloride peak and the triprolidine hydrochloride cis isomer peak should be greater than 10. Precisely measure 10 µl each of the test solution, control solution and impurity reference solution, and inject them into the liquid chromatograph respectively. Record the chromatogram to 3 times the peak retention time of the main component. The chromatograms of the test solution have peaks consistent with the retention time of triprolidine hydrochloride cis-isomer. The peak area calculated according to the external standard method shall not exceed 1.0%; the peak area of other single impurities shall not be larger than the control. The main peak area of the solution (1.0%); the total amount of impurities must not exceed 2.0%. ^[2]

3 residual solvents

Take about 0.2g of this product, weigh it accurately, place it in a headspace bottle, add 5ml of water to dissolve it, seal it, and use it as a test solution. Weigh each appropriate amount of methanol and ethyl acetate precisely and dilute with water to make about 1ml. A mixed solution containing 0.12 mg of methanol and 0.2 mg of ethyl acetate, 5 ml was accurately measured, placed in a headspace bottle, sealed, and used as a reference solution. According to the residual solvent determination method (Chinese Pharmacopoeia 2015 Edition Four General Rules 0861 second method), the capillary column with 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polarity) as the fixing solution is Chromatographic column; the initial temperature is 100 ° C for 5 minutes, and then heated to 220 ° C at a rate of 60 ° C per minute for 2 minutes; the detector is a hydrogen flame ionization detector (FID), and the detector temperature is 250 ° C; The inlet temperature was 200 ° C. The headspace bottle equilibrium temperature was 80 ° C and the equilibration time was 30 minutes. Take the reference solution headspace sample and record the chromatogram. The peaks should be in the order of methanol and ethyl acetate. The resolution between the two peaks should meet the requirements. Then take the test solution and the reference solution for headspace injection, record the chromatogram, and calculate the peak area according to the external standard method. The residual amounts of methanol and ethyl acetate should meet the requirements. ^[2]

4 moisture

Take this product and measure it according to the moisture determination method (Chinese Pharmacopoeia 2015 Edition Four General Rules 0832 first method 1), the moisture content should be 4.0% ~ 6.0%. ^[2]

5 burning residue

Take 1.0g of this product and check it according to law (General Regulations of the Fourth Section of the Chinese Pharmacopoeia 2015 Edition 0841). The residual residue shall not exceed 0.1%. The heavy metal is taken from the residue left under the burning residue, and shall be inspected according to law (the second law of General Regulation 0821 of the Fourth Edition of the Chinese Pharmacopoeia 2015), and it shall not contain more than 20 parts per million. ^[2]

Determination of triprolidine

Take about 0.26g of this product, accurately weigh, add 50ml of ethanol and 5.0ml of 0.01mol / L hydrochloric acid solution, shake to dissolve. Potentiometric titration method (Chinese Pharmacopoeia 2015 edition four general rules 0701), titration with sodium hydroxide titration solution (0.1mol / L), recording the volume difference of the titration solution consumed at two jump points. Each 1ml of sodium hydroxide titration solution (0.1mol / L) is equivalent to 31.48mg of C19H22N2 · HCl. ^[2]

Triprolidine pharmacological effects

This product is a piperidine antihistamine. It competes with histamine for H1 receptors on effector cells in the body, which completely eliminates the opportunity for histamines to bind to H1 receptors, thereby inhibiting the occurrence of allergic reactions. Therefore, this product has a high selectivity for blocking the H1 receptor, and it has not been found to have other pharmacological effects. This product has the characteristics of strong, long-acting, low toxicity and no central inhibitory adverse reactions. ^[3]

Triprolidine pharmacokinetics

This product is quickly and completely absorbed orally. It takes effect about 30 minutes after administration, with a tmax of 1 to 3 hours, a half-life of 14 ± 2 hours, and a duration of action of 8 to 12 hours. Widely distributed in the body, the local concentration is higher in lung, spleen and kidney. It is mainly metabolized by the liver and decomposed into toluene-based degradation products, which are excreted in the urine. This product rarely penetrates the blood-cerebrospinal fluid barrier. ^[3]

Triprolidine indications

It is used to treat allergic diseases, including allergic rhinitis, urticaria, allergic conjunctivitis, pruritus of the skin, etc. ^[4]

Triprolidine specifications

2.5 mg ^[4]

Triprolidine dosage

oral. Adults 2.5 mg to 5 mg (1-2 capsules) each time, 2 times a day. ^[4]

Triprolidine adverse reactions

This product occasionally has adverse reactions such as nausea, tiredness, dry mouth, mild drowsiness, etc., which can disappear by itself after reduction or withdrawal. ^[4]

Triprolidine contraindications

Patients with acute asthma attacks, premature babies and newborns, lactating women are prohibited. ^[4]

Triprolidine precautions

1. Increased intraocular pressure, angle-closure glaucoma, hyperthyroidism, vascular disorders and hypertension, bronchial asthma, prostatic hyperplasia, bladder neck obstruction, peptic ulcers, and children under 12 years of age should be used with caution.

2. Pregnant women and the elderly should be used under the guidance of a physician.

3 Do not drive machines, cars, ships, engage in high-altitude operations, mechanical operations, or operate precision instruments during medication.

4 Those who are allergic to this product are prohibited, and those with allergies should use it with caution.

5. It is forbidden to use this product when its properties change.

6. Keep this product out of the reach of children.

7. Children must be used under adult supervision.

8. If you are using other medicines, please consult your physician or pharmacist before using this product. ^[4]

Triprolidine drug interactions

1. Do not take monoamine oxidase (MAO) inhibitors, central sedative or hypnotics, and alcoholic beverages at the same time.

2. Drug interactions may occur if used concurrently with other drugs, please consult your physician or pharmacist for details. ^[4]

Triprolidine storage

Protected from moisture and light, sealed in a cool (not more than 20 ° C) dry place. ^[4]