Forced degradation studies of rapamycin: identification of autoxidation products.

The immunosuppressant drug rapamycin, also known as Sirolimus, underwent autoxidation under mild conditions to give numerous monomeric and oligomeric compounds, which were generally characterized by size-exclusion chromatography and NP-HPLC with UV and MS detection. Some of the more predominant products, epoxides and ketones, were isolated and identified. Two epoxides and 10S-epimer of rapamycin were described for the first time.

Mass balance in rapamycin autoxidation.

The immunosuppressant drug rapamycin is a complex polyene-containing natural product which undergoes autoxidation. The resulting product mixtures contained numerous monomeric and oligomeric compounds, which represented challenges for addressing mass balance in forced degradation studies and in analysis of aged developmental drug-eluting stents. A combination of SEC with ultraviolet and refractive index detection and RP-HPLC was used to account for drug loss and product formation.

Degradation chemistry of a Vitamin D analogue (ecalcidene) investigated by HPLC-MS, HPLC-NMR and chemical derivatization.

Ecalcidene (1-[(1alpha,3beta,5Z,7E,20S)-1,3-dihydroxy-24-oxo-9,10-secochola-5,7,10(19)-trien-24-yl]-piperidine) is a new 1-hydroxyvitamin D analogue. In this report, the thermal degradation, acid induced degradation and iodine induced degradation of ecalcidene were investigated using HPLC-MS, HPLC-NMR and chemical derivatization. In solution ecalcidene was thermally and reversibly transformed to a pre-Vitamin D type isomer 1 which subsequently produced the dehydrated pyrocalciferol and isopyrocalciferol type isomers 2 and 3 by cyclization and dehydration at elevated temperatures.

Detection of choline and acetylcholine in a pharmaceutical preparation using high-performance liquid chromatography/electrospray ionization mass spectrometry.

A sensitive, rapid, and specific method for the detection of choline and acetylcholine in a pharmaceutical preparation is described. The method employs a perfluorinated carboxylic acid as ion-pairing reagent, post-column addition of a surface tension reducing agent and mass spectrometric detection using either selected ion monitoring (SIM) or selected reaction monitoring (SRM) modes. The resulting chromatographic performance is comparable or superior to methods reported previously in both quality of the separation and sensitivity when using mass spectral detection, with the added advantage of reduced cycle time.