The practical application of implementing the equimolar response principle of chemiluminescent nitrogen detection in pharmaceutical analysis.
Since nearly 90% of all developmental and marketed drugs contain at least one nitrogen atom, the implementation of chemiluminescent nitrogen detection (CLND) in pharmaceutical analysis is intriguing due to its equimolar response for nitrogen. Although the documented accuracy of CLND when using a surrogate nitrogen-containing standard may be inadequate for purity and potency determinations, it is acceptable for the quantitation of low-level impurities. A comparison of the quantitative results obtained using both CLND and UV detection for a developmental drug and its related impurities is presented. The results indicated that the impurities can be accurately quantified using a surrogate standard, based on the equimolar response principle of CLND, when the concentrations of the surrogate standard and the component of interest are similar. When the impurities are present at much lower levels than the surrogate standard however, the common practice of direct conversion of area percent to weight percent can result in significant errors using CLND, due to the limited linear dynamic range for CLND. To increase quantitation accuracy, the authors propose that a secondary dilution of the surrogate reference standard solution should be used for the quantitation of low-level impurities. The practical application of this approach for impurity quantitation or as a means to determine impurity relative response factors for use with a traditional UV based method is discussed.
Liang
X
X
Analytical R&D, Bristol Myers Squibb Co., New Brunswick, NJ 08903, USA. xiaozhong.liang@bms.com
Patel
H
H
Young
J
J
Shah
P
P
Raglione
T
T
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004340:Drug Contamination / Q000517:prevention & control; D006801:Humans; D008163:Luminescent Measurements; D008970:Molecular Weight; D009584:Nitrogen / Q000032:analysis* / Q000737:chemistry; D004364:Pharmaceutical Preparations / Q000032:analysis*; D012015:Reference Standards; D013056:Spectrophotometry, Ultraviolet
D004364:Pharmaceutical Preparations; D009584:Nitrogen