Triprolidine hydrochloride

Actifed is a medicinal preparation in which the effective components are the two drugs pseudoephedrine hydrochloride and triprolidine hydrochloride. The absorption spectrum of Actifed tablets dissolved in 0.1M hydrochloric acid is similar to that shown in Fig. 17.14(a) which is clearly of no value for quantitative determinations. A second derivative spectrum however is similar in character to that shown in Fig. 17.14(6) in which peak C corresponds to the pseudoephedrine hydrochloride and D to the triprolidine hydrochloride and from which it is possible to make quantitative measurements. Experience showed that it is advisable to use different response times for the two peaks with the instrument used a response setting of 3 was found to give the best results for pseudoephedrine hydrochloride, whilst a setting of 4 was best for the triprolidine hydrochloride. 

Triprolidine hydrochloride is E-2-[3-(l-pyrroli-dinyl)-l-p-tolylpropenyl]pyridine, monohydrochloride E-l-(2-pyridyl)-3-pyrrolidino-l-p-tolylprop-l-ene, monohydrochloride. ... 

Triprolidine hydrochloride occurs as a white, crystalline powder, with no more than a slight unpleasant odor.1... 

The infrared spectrum of triprolidine hydrochloride is shown in Figure 1. The IR spectrum was recorded with a Nicolet model 7199 FT-IR spectrophotometer as a 0.2% dispersion of triprolidine hydrochloride in KBr.2 Table I gives the infrared assignments consistent with the structure of triprolidine hydrochloride. 

Infrared Spectral Assignments for Triprolidine Hydrochloride Monohydrate... 

The NMR spectrum of triprolidine hydrochloride is shown in Figure 2. It was obtained with a Varian XL-100 100 MHz NMR spectrometer. Deuterated DMS0 was used as the solvent with tetramethylsilane as an internal standard.3 The interpretation of the NMR spectrum is given in Table II. 

Figure 2 - Nuclear Magnetic Resonance Spectrum Triprolidine Hydrochloride... 

NMR Assignments for Triprolidine Hydrochloride Chemical Shift (ppm) No. of Protons Multiplicity Assignments... 

The ultraviolet spectrum of triprolidine hydrochloride in 0.1N HC1 was taken with a Beckman ACTA CIII UV spectrophotometer and is shown in Figure 3.4 Table III gives the UV data for triprolidine hydrochloride in various solvents. 

The mass spectrum of triprolidine hydrochloride is shown in Figure 4. It was obtained with a Varian MAT CH5-DF mass spectrometer. The electron energy was 70 eV and the sample was introduced via direct probe at 120°C.5 The characteristic fragments are in agreement with those found by Kuntzman and co-workers.6 The major fragments characteristic of triprolidine are shown in Figure 5. 

Triprolidine hydrochloride in 0.1M sulfuric acid has an excitation maximum at 305 nm and an emission maximum at 445 nm. The fluorescence is much diminished in hydrochloric acid and almost non-existent in distilled water. 

The addition of halide ions to 0.1M sulfuric acid solutions of triprolidine hydrochloride has a quenching effect on the fluorescent intensity. The degree of quenching is I > Br >C1 > F. A concentration of 10 M Cl has little effect on the fluorescent intensity, while 0.1M Cl reduces the intensity by approximately 75% of the chloride-free sulfuric acid solution. 

James and Williams have determined that triprolidine hydrochloride monohydrate crystals belong to the P2j/c space group.8 There are 4 molecules per unit cell. The... 

Figure 5 - Major Ions in Mass Spectrum of Triprolidine Hydrochloride...

Triprolidine hydrochloride melts at 115-120°C in a sealed capillary tube.9... 

The solubility of triprolidine hydrochloride, as the monohydrate, in various solvents at 25°C is given in Table IV.9... 

The partition coefficients of triprolidine hydrochloride in n-octanol/aqueous pH 1.2 and n-octanol/aqueous pH 7.4 are 0.041 and 7.0 respectively.9... 

The synthesis of triprolidine hydrochloride is shown in Figure 6.10 The 4-methyl-u>-pyrrolidinopropio-phenone used in the first step is prepared by the Mannich... 

Ultraviolet light will convert the E-form of triprolidine hydrochloride to the Z-form. After 2 years at 37°C, triprolidine hydrochloride in a syrup formulation does not decompose more than 10%. After 3 years at 37°C triprolidine hydrochloride in tablet formulations does not decompose more than 10%. The formulations are kept in light resistant containers since triprolidine hydrochloride discolors on exposure to light.9... 

Figure 7 shows the major metabolic pathway of triprolidine hydrochloride as determined in a study of 14C labelled triprolidine hydrochloride in guinea pigs.6 Triprolidine is converted to metabolite I by liver microsomes. Metabolite I is converted to metabolite II which is the major metabolite found in guinea pig urine. 

The plasma levels of triprolidine hydrochloride were determined in 16 normal male subjects.12 When administered orally at a concentration of 3.75 mg triprolidine hydrochloride in 15 ml of syrup, peak plasma levels of 8.2 ng/ml were achieved in 2 hours with a drug half-life of 5 hours. The low plasma levels found indicate a large volume of tissue distribution which was consistent with data obtained from rat studies. 

The results of the elemental analysis of triprolidine hydrochloride are given in Table V.3 The theoretical... 

Elemental Analysis of Triprolidine Hydrochloride Element Theory (%) Found (%) ... 

Triprolidine hydrochloride is dissolved, with warming if necessary, in glacial acetic acid. Mercuric acetate test solution is added and the solution titrated with 0.1N perchloric acid, the end-point being determined potentiometrically. Each ml. of 0.1N perchloric acid is equivalent to 0.05 mmole of triprolidine hydrochloride.1... 

An ultraviolet spectrophotometric analysis is used to determine content uniformity of triprolidine hydrochloride in tablet formulations.1 The triprolidine hydrochloride is extracted from finely powdered tablets with dilute hydrochloric acid. The solution is filtered and diluted to a concentration of approximately 10 Jg triprolidine hydrochloride per ml. The absorbance at 290 nm of the extracted triprolidine hydrochloride solution in 1 cm cells is compared against NF Triprolidine Hydrochloride Reference Standard prepared in dilute hydrochloric acid at the 10 pg/ml level. 

Triprolidine hydrochloride has been separated from other antihistamines with a 1.52m x 2.4 mm i.d. column packed with 2% carbowax 20M + 10% KOH on 60/80 mesh Chromosorb W. Retention time of 32 minutes was obtained with a column temperature of 190°C. Triprolidine hydrochloride was probably eluted as the free base.21... 

Triprolidine hydrochloride in syrups and tablets can be analyzed by fluorimetry. A portion of the tablets or syrup is made basic with IN NaOH and extracted with ethylene chloride. The organic phase is then extracted with 0.1N I SO. The fluorescence of the acid extract is determined with a fluorometer using a UG11 filter for excitation and a Wratten 2A filter for emission. The fluorescence of the sample preparation is compared against a Reference Standard prepared in the same manner22. 

Trimethaphan camsylate, 3,545 Trimethobenzamide hydrochloride, 2,551 Trimethoprim, 7,445 Triprolidine hydrochloride, 8,509 Tropicamide, 3,565 Tubocurarine chloride, 7,477 Tybamate, 4,494... 

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