Simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations by liquid chromatography

Urbáanyi, T.; Piedmont, A.; Willis, Edward; Manning, Georgina

doi:10.1002/jps.2600650220

Cited by 26 publications

(3 citation statements)

References 7 publications

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“…Pilocarpine nitrate (Sigma Chemical, St. Louis, MO) was assayed for possible isopilocarpine contamination by the method of Urbanyi et al (1976), determined to be > 99% pure, and used without further purification. Sodium pentobarbital (64 mg/mL, Fort Dodge, IA) and atropine (1 mg/ mL, Elkin-Sinn, Cherry Hill, NJ) were sterile solutions.…”

Section: Methodsmentioning

confidence: 99%

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

1992

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We tested whether permucosal delivery of pilocarpine nitrate could be used to elicit significant salivary secretion. Pilocarpine (pKa 6.6 at 37 degrees C) was applied as solutions (pHs 5.6, 6.6, 7.6; 15 mg/mL) to the buccal mucosa (2.8 cm2) of 6 anesthetized dogs. Saliva was collected continuously from cannulated submandibular and parotid ducts and blood sampled during and after drug administration. Plasma pilocarpine levels were determined by reversed-phase HPLC. Absorption rates were determined by use of data from separate zero-order intravenous infusions to the same dogs. Pilocarpine was buccally absorbed at a constant rate of 72.9 +/- 38.5 micrograms/kg/h following its application at pH 7.6. At this pH of the drug solution, the time to appearance of pilocarpine in blood plasma was 0.31 +/- 0.08 h, and the time to appearance of salivary flow was 0.86 +/- 0.32 h. A threshold dose of 32.9 +/- 7.5 micrograms/kg was required to induce secretion with the pH 7.6 drug, the steady-state submandibular flow rate was 0.14 +/- 0.11 mL/min/gland pair. Salivary flow induction was symmetrical and reached levels as high as 0.35 mL/min/submandibular gland pair without apparent tachyphylaxis. Results at pHs 5.6, 6.6, and 7.6 were consistent with the hypothesis that pilocarpine is primarily absorbed as un-ionized drug. The data indicate that transmucosal delivery of pilocarpine, avoiding "first pass" hepatic loss, may hold promise for the treatment of xerostomia.

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Section: Methodsmentioning

confidence: 99%

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

1992

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“…From a survey of the literature it appears that most of these use reversed-phase chromatography on phenyl-bonded or octadecyl-bonded silica and concentrated salt buffers containing phosphate, sulphate and low concentrations of an organic solvent (methanol or acetonitrile) [4 9-11 16-25]. An ion-exchange system [26], a straightphase system [27] and two ion-pair reversedphase systems [9 28] have also been described. The resolution of pilocarpine from its diastereomer isopilocarpine constitutes a major problem which has been solved by prolonging the elution time or by analysing these epimers in a separate run under special chromatographic conditions [19 22 26 27].…”

Section: Introductionmentioning

confidence: 98%

Decomposition of pilocarpine eye drops assessed by a highly efficient high pressure liquid chromatographic method

Kuks

Weekers

Goldhoorn

1990

Pharmaceutisch Weekblad Scientific Edition

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A rapid high-resolution high pressure liquid chromatographic method was developed for assaying pilocarpine. Pilocarpine in ophthalmic solutions decomposes fairly rapidly to give isopilocarpine, pilocarpic acid and isopilocarpic acid. The quality of an ophthalmic solution can be assessed by assaying these decomposition products. Existing high pressure liquid chromatographic methods suffer from long analysis times and poor resolution. The new method uses as the mobile phase 6 ml/l of triethylamine in water (pH 2.3, adjusted with 85% phosphoric acid) at a flow of 1.5 ml/min and as the stationary phase a C18-silica 125 x 4.6 mm column. 2-Amino-1-phenyl-1,3-propanediol is used as an internal standard. Complete separation was obtained within 8 min. Pilocarpine eye drops were stored under different conditions and then analysed for decomposition products. During heat treatment, decomposition to isopilocarpine predominated over decomposition to pilocarpic or isopilocarpic acid. However, when stored at room temperature or in a refrigerator, formation of pilocarpic acid clearly prevailed. Thus, from assessment of decomposition products, the cause of decomposition can be established.

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“…Since the moiety responsible for producing color is an intact lactone ring, the assay can distinguish between pilocarpine and pilocarpic acid but not between pilocarpine and isopilocarpine (4). This flaw is serious since recent studies indicated that the primary degradation product of pilocarpine is not pilocarpic acid but ita diastereomer, isopilocarpine (4).…”

Section: Introductionmentioning

confidence: 99%

Analysis of Pilocarpine and Isopilocarpine in Ophthalmic Solutions by Normal-Phase High-Performance Liquid Chromatography

Dunnx

Scott

Dorsey

1981

Journal of Pharmaceutical Sciences

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Simultaneous determination of pilocarpine and isopilocarpine in pharmaceutical preparations by liquid chromatography

Cited by 26 publications

References 7 publications

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

Salivary Flow Induction by Buccal Permucosal Pilocarpine in Anesthetized Beagle Dogs

Decomposition of pilocarpine eye drops assessed by a highly efficient high pressure liquid chromatographic method

Analysis of Pilocarpine and Isopilocarpine in Ophthalmic Solutions by Normal-Phase High-Performance Liquid Chromatography

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