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

Bioisosterism: A Rational Approach in Drug Design

“…Pilocarpine ( 58 , Figure ) is widely employed as a topical miotic for controlling the elevated intraocular pressure associated with glaucoma. The duration of lowering of intraocular pressure by pilocarpine lasts only for about 3 h. This short duration of action is mainly due to the hydrolytic cleavage of the lactone ring, resulting in the formation of pilocarpic acid and rapid elimination and/or epimerization to form isopilocarpine . In an attempt to study the influence of the carbamate nitrogen on physiological properties, certain carbamate analogues corresponding to pilocarpine were synthesized and evaluated …”

“…The duration of lowering of intraocular pressure by pilocarpine lasts only for about 3 h. This short duration of action is mainly due to the hydrolytic cleavage of the lactone ring, resulting in the formation of pilocarpic acid and rapid elimination and/or epimerization to form isopilocarpine. 65 In an attempt to study the influence of the carbamate nitrogen on physiological properties, certain carbamate analogues corresponding to pilocarpine were synthesized and evaluated. 66 Replacement of the carbon atom on the oxazolidinone ring with nitrogen resulted in the carbamate analogue 59 which was equipotent with pilocarpine (ED 50 ) 1 µM).…”

Bioisoterism Review- An Biological Modification

“…The duration of lowering of intraocular pressure by pilocarpine lasts only for about 3 h. This short duration of action is mainly due to the hydrolytic cleavage of the lactone ring, resulting in the formation of pilocarpic acid and rapid elimination and/or epimerization to form isopilocarpine [31] In an attempt to study the influence of the carbamate nitrogen on physiological properties, certain carbamate analogues corresponding to pilocarpine were synthesized and evaluated. [32] Replacement of the carbon atom on the oxazolidinone ring with nitrogen resulted in the carbamate analogue which was equipotent with pilocarpine (ED50 =1μM).…”

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

“…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].…”