Degradation and impurity analysis for pharmaceutical drug candidates

Alsante, Karen M.; Friedmann, Robert C.; Hatajik, Todd D.; Lohr, Linda; Sharp, Thomas R.; Snyder, Kimberly D.; Szczesny, Edward J.

doi:10.1016/s0149-6395(01)80006-4

Cited by 37 publications

(47 citation statements)

References 52 publications

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“…The structural differences were determined through a structural analysis of ascomycin and tacrolimus using 13 C-NMR assignments. Through LC-MS/MS analysis, the results of the molecular information were combined, and it was found that 18-methyltacrolimus has not yet been reported.…”

Section: Resultsmentioning

confidence: 99%

“…These differences were determined on the basis of the 13 C-NMR peak assignments by following the location of the methyl group identified by analysis of the chemical structure.…”

Section: Resultsmentioning

confidence: 99%

“…In all cases, the impurities should be qualified. NMR spectrometer (advance NMR spectrometer, Bruker, 400 MHz) was used with 1 H, 13 C nucleous and chloroform-d were used as dissolution solvents. To establish the analytical conditions of the unknown derivative powder (purity: 90%, 15 mg), the previous studies on structural analysis were used as reference.…”

mentioning

confidence: 99%

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Identification of an 18-Methyl Derivative of Tacrolimus API in Streptomyces clavuligerus CKD-1119

Ham¹,

Koo

2011

Bulletin of the Korean Chemical Society

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A new derivative of tacrolimus was evaluated for its molecular weight, using LC-MS of the tacrolimus bulk active pharmaceutical ingredient (API) recovered through the purification of crude tacrolimus produced by Streptomyces clavuligerus CKD-1119. In addition, the molecular weight of the new derivative of tacrolimus was found to be at m/z 818 and was identified by 13 C-NMR with peak assignments based on the differences in methyl group location resulting from the chemical structure. The structure of the new derivative, an unknown impurity of tacrolimus, was found to be 18-methyltacrolimus through comparison of the spectral data of the structural differences between ascomycin, tacrolimus, and the new derivative 18-methyltacrolimus.

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Section: Resultsmentioning

confidence: 99%

“…These differences were determined on the basis of the 13 C-NMR peak assignments by following the location of the methyl group identified by analysis of the chemical structure.…”

Section: Resultsmentioning

confidence: 99%

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Identification of an 18-Methyl Derivative of Tacrolimus API in Streptomyces clavuligerus CKD-1119

Ham¹,

Koo

2011

Bulletin of the Korean Chemical Society

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“…A number of recent articles 7,8 described a designed approach and guidance for the isolation and identification of process-related impurities and degradation products. In general, according to ICH guidelines on impurities in new drug products 9 , identification of impurities below the 0.1 % level is not considered to be necessary unless the potential impurities are expected to be unusually potent or toxic.…”

Section: Issn: 0975-8232mentioning

confidence: 99%

Untitled

2012

IJPSR

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“…In addition, a number of recent articles [4][5][6] have described a designed approach and guidance for isolating and identifying process-related impurities and degradation products using MS, NMR, HPLC, Fourier transform ion cyclotron resonance MS (FTICR-MS), and MS/MS for pharmaceutical substances. These have been reviewed by Roy [7].…”

Section: Introductionmentioning

confidence: 99%

CE as orthogonal technique to HPLC for alprazolam degradation product identification

et al. 2006

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The control of degradation products is currently a critical issue to the pharmaceutical industry. A degradation product that appeared in alprazolam tablets during their stability assay, 7-chloro-1-methyl-5-phenyl-[1,2,4]triazolo[4,3-a]quinolin-4-amine, also named triazolaminoquinoline, was tested as possible candidate in the HPLC method employed for the study. The impurity showed the same retention time and spectra as the degradation product; but as all these compounds are very closely related, a confirmation with an independent technique was necessary, and CE was chosen for that purpose. Problems related to the adsorption of the analytes to the negatively charged silica surface were solved by employing a new polymeric capillary coating consisting of poly(3-aminopropylmethylsiloxane). The polymer provided EOF towards the anode, and the two compounds were separated in less than 8 min in a 60 cm total-length capillary, 75 microm id capillary with a BGE containing 50 mM phosphate buffer at pH 2.0 with 20% ACN. When the sample containing the degradation product was injected, the presence of triazolaminoquinoline was confirmed.

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Degradation and impurity analysis for pharmaceutical drug candidates

Cited by 37 publications

References 52 publications

Identification of an 18-Methyl Derivative of Tacrolimus API in Streptomyces clavuligerus CKD-1119

Identification of an 18-Methyl Derivative of Tacrolimus API in Streptomyces clavuligerus CKD-1119

Untitled

CE as orthogonal technique to HPLC for alprazolam degradation product identification

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