Method for enantiomeric purity of a quinuclidine candidate drug by capillary electrophoresis.

A chiral procedure based on EKC was developed and validated for determination of the enantiomeric purity of PHA-543613, a drug candidate that was under development for treatment of the cognitive deficits of Alzheimer's disease and schizophrenia. Separation of enantiomers is accomplished via differential, enantiospecific complexation with a single-isomer, precisely sulfated beta-CD and heptakis-6-sulfato-beta-CD (HpS-beta-CD). Both neutral and sulfated CDs were screened before selecting HpS-beta-CD as the chiral selector.

Enantiomeric purity methods for three pharmaceutical compounds by electrokinetic capillary chromatography utilizing highly sulfated-gamma-cyclodextrin as the chiral selector.

Methods for enantiomeric purity by electrokinetic chromatography were developed and validated for three pharmaceutical compounds, each utilizing highly sulfated-gamma-cyclodextrin (HS-gamma-CD) as the chiral recognition agent. Two of the compounds are weak bases, hence charged at low pH, and the third is a quaternary nitrogen compound, charged at all pH. In each instance quantification was via an authentic reference standard with addition of an internal standard.

Determination of the molecular complexation constant between alprostadil and alpha-cyclodextrin by conductometry: implications for a freeze-dried formulation.

The binding constant between alprostadil (PGE1) and alpha-cyclodextrin (alpha-CD) was determined at four temperatures using conductance measurements. Alpha-cyclodextrin is an excipient material in Caverject dual chamber syringe (DCS) that was added to enhance stability. The binding constant was used to calculate the amount of PGE1 free upon reconstitution and injection, since only the free drug is clinically active.

A method for the determination of minoxidil in hair-regrowth formulations by micellar electrokinetic capillary chromatography.

A method based on micellar electrokinetic capillary chromatography (MEKC) was developed for determination of minoxidil in Rogaine and competing products. The original intent of the work was to offer an orthogonal means to HPLC for testing illicit imitations of Rogaine. However, because the patent has since expired, we offer the procedure as a confirmatory measure to HPLC for assay of generic minoxidil products.

Rapid determination of trace amounts of minoxidil in hamster skin follicles with various formulations using narrow-bore LC/EC.

A sensitive liquid chromatographic method with electrochemistry (LC/EC) was developed for the determination of trace of minoxidil in hamster skin follicles after topical administration of the ear using various formulations. The minoxidil in the sebaceous glands of the hamster ear was isolated from the skin and the follicles in different skin layers were treated with aqueous trichloroacetic acid followed by acetonitrile. The supernatant was directly injected into the LC/EC system and minoxidil was detected by oxidation at +800 mV versus Ag/AgCl using a glassy carbon electrode.

Determination of the binding constant between alprostadil and alpha-cyclodextrin by capillary electrophoresis: implications for a freeze-dried formulation.

The binding constant between alprostadil (PGE1) and alpha-cyclodextrin (alpha-CD) was determined at three temperatures by capillary electrophoresis. alpha-CD is an excipient material in Caverject Dual Chamber Syringe (DCS), added to enhance stability. The binding constant was used to calculate the amount of PGE1 free upon reconstitution and injection, the latter of which is critical to product performance.

Determination by NMR of the binding constant for the molecular complex between alprostadil and alpha-cyclodextrin. Implications for a freeze-dried formulation.

A binding constant was determined for the complexation reaction between alprostadil (PGE1) and alpha-cyclodextrin (alpha-CD). This constant was used to calculate the fraction PGE1 free upon reconstitution of Caverject dual chamber syringe, indicated for the treatment of erectile dysfunction. The determination was based on the measurement of the chemical shift of the C20 methyl protons of PGE1.

Determination of protein-drug binding constants by pressure-assisted capillary electrophoresis (PACE)/frontal analysis (FA).

A simple method for the determination of binding constants of drugs to human serum albumin (HSA) and alpha(1)-acid glycoprotein (AGP) was developed by pressured-assisted capillary electrophoresis (PACE) based on the principle of frontal analysis (FA). The free drug concentration was measured from the height of the frontal peak and calculated based on the external drug standard in the absence of protein. With a known concentration of total drug, the percentage of drug bound to HSA or AGP was then determined.