Impurity profile tracking for active pharmaceutical ingredients: case reports.
Tracking the impurity profile of an active pharmaceutical ingredient (API) is a very important task for all stages of drug development. A systematic approach for tracking impurity profile of API is described. Various real pharmaceutical applications are presented through successful examples of impurity profile tracking for three different novel APIs. These include MK-0969, an M3 antagonist; MK-0677, an oral-active growth hormone secretagogue and API-A, a cathepsin K inhibitor. A general strategy including selection of a reversed phase high performance liquid chromatographic (RP-HPLC) impurity profile method based on screening various stationary phases and changing the pH of the mobile phase and elucidation of impurity structures through the utilization of LC-MS, preparative-LC and NMR is demonstrated. A series of studies were conducted on the peak purity check by using the LC-UV diode-array and LC-MS detections. The advantages and disadvantages of each technique in the evaluation of peak purity are discussed.
Zhou
Lili
L
Merck Research Laboratories, Early Development Analytical Research, P.O. Box 2000, RY818-B225, Rahway, NJ 07065, USA. lili_zhou@merck.com
Mao
Bing
B
Reamer
Robert
R
Novak
Tom
T
Ge
Zhihong
Z
D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination; D004345:Drug Industry; D004791:Enzyme Inhibitors / Q000032:analysis; D019382:Human Growth Hormone / Q000819:agonists; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000032:analysis; D018727:Muscarinic Antagonists / Q000032:analysis; D004364:Pharmaceutical Preparations / Q000032:analysis*; D043587:Receptor, Muscarinic M3 / Q000037:antagonists & inhibitors; D013056:Spectrophotometry, Ultraviolet; D013141:Spiro Compounds / Q000032:analysis
D004791:Enzyme Inhibitors; D007211:Indoles; D018727:Muscarinic Antagonists; D004364:Pharmaceutical Preparations; D043587:Receptor, Muscarinic M3; D013141:Spiro Compounds; D019382:Human Growth Hormone; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C094817:ibutamoren mesylate