Strategies for the investigation and control of process-related impurities in drug substances☆

Argentine, Mark D.; Owens, Paul K.; Olsen, Bernard A.

doi:10.1016/j.addr.2006.10.005

Cited by 78 publications

(37 citation statements)

References 66 publications

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“…Other literature also has reported studies of HPLC-UV and HPLC-MS for therapeutic drug monitoring of everolimus [26,27]. As indicated, a strategy for process impurity tracking is generally via molecular ion identification [14,28]. In this complex ABT-578 process, tracking and mapping impurities of numerous isomers/epimers (co-elution) with mainly a MS/MS approach is simply not realistic or useful.…”

Section: Ms Detection Examplesmentioning

confidence: 95%

Normal phase and reverse phase HPLC-UV-MS analysis of process impurities for rapamycin analog ABT-578: Application to active pharmaceutical ingredient process development

Chen

Brill

Benz

et al. 2007

Journal of Chromatography B

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Section: Ms Detection Examplesmentioning

confidence: 95%

Normal phase and reverse phase HPLC-UV-MS analysis of process impurities for rapamycin analog ABT-578: Application to active pharmaceutical ingredient process development

Chen

Brill

Benz

et al. 2007

Journal of Chromatography B

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“…The potential impurities may be available from the vendor, purchased if commercially available or synthesized. Waste streams, mother liquors and degraded samples may offer additional opportunities to gain knowledge on impurities and their monitoring [9].…”

Section: Introductionmentioning

confidence: 99%

“…It should be noted that for a number of samples a single technique is not able to provide a complete impurity profile, whereas this could be achieved using a combination of techniques. Although RPLC is the main analytical method recommended by different pharmacopeia (its applications in impurity analysis of pharmaceuticals were reviewed by Nageswara Rao and Nagaraju [8]), the significance of other techniques is not less than RPLC, especially when the orthogonality concept is considered [9]. Orthogonality can be achieved when analytical techniques with different mechanisms are combined, e.g.…”

Section: Introductionmentioning

confidence: 99%

Impurity analysis of pharmaceuticals using capillary electromigration methods

Jouyban

Kenndler

2008

Electrophoresis

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This review deals with the determination of impurities in pharmaceuticals by electromigration methods in the capillary format. These separation methods are either based on the different effective mobility of the charged analytes (as in zone electrophoresis and isotachophoresis) or include hybrid methods such as micellar electrokinetic chromatography, microemulsion electrokinetic chromatography and electrochromatography. The pharmaceutically active compounds under consideration belong to chemotherapeutic agents, central nervous system drugs, histamine receptor drugs, cardiovascular drugs, anticancer drugs, anti-inflammatory drugs and some other drugs. The review discusses about 150 publications from the period between 1980 and 2007 with special emphasis on the recent trends and gives details about the experimental conditions applied for analyses and the obtained analytical performance parameters.

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“…Although HPLC is the main analytical method recommended by different pharmacopeia, other techniques are valid, especially when the orthogonality concept is considered. 15) Orthogonality can be achieved when the findings of analytical techniques with different mechanism are combined, e.g., CE with HPLC.…”

mentioning

confidence: 99%

Analysis of Oseltamivir in Tamiflu Capsules Using Micellar Electrokinetic Chromatography

Jabbaribar

Mortazavi

Jalali-Milani³

et al. 2008

CHEMICAL & PHARMACEUTICAL BULLETIN

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1639Oseltamivir (Ro 64-0796 or GS4104) is an ethyl ester prodrug of oseltamivir carboxylate (Ro 64-0802 or GS4071) with the chemical name of ethyl (3R,4R,5S)4-acetylamino 5-amino-3(1-ethylpropoxy)1-cyclohexene-1-carboxylate phosphate (1 : 1). Its chemical structure is shown in Fig. 1. It inhibits neuraminidase activity in influenza A and B viruses. The activity of the enzyme is essential for the spread of infectious virus in the body. Oseltamivir is an effective therapeutic agent against pandemic influenza strains, including H5N1 that caused pandemics during recent years around the world. Since 2003, H5N1 has had a devastating impact on domestic and wild bird populations in many parts of Southeast Asia, Europe, the Middle East, and some parts of Africa. The virus was transmitted to humans, infecting more than 230 people, of whom over 50% died. 1)Oseltamivir is prescribed for both the treatment and prevention of influenza and is marketed as its phosphate salt by Roche Company under the trade name, Tamiflu ® . Tamiflu ® is available in both capsule and oral suspension formulations. In addition, the drug is supplied as an active pharmaceutical ingredient (API) for pandemic stockpiling. The API can be dissolved in water and distributed for widespread use in a pandemic outbreak. Brewster et al. showed the bioequivalence of API solution and capsule formulation.2) Oseltamivir is rapidly hydrolyzed in vivo to oseltamivir carboxylate by hepatic carboxylesterase. Both the prodrug and oseltamivir carboxylate are excreted unchanged in the urine.3) Bioassay,4) chromatographic methods with fluorescence, 5) mass spectrometric 6,7) and UV 8-13) detection have been described for the analysis of oseltamivir, but to the best of our knowledge, there is no report on the capillary electrophoresis (CE) method for the analysis of oseltamivir. To provide more information on the reported methods to analyze oseltamivir and its hydrolytic product, the related articles are briefly reviewed in chronological order. Eisenberg and Cundy 5) reported an HPLC method for the analysis of oseltamivir carboxylate in rat plasma using pre-column derivatization with naphthalendialdehyde and fluorescence detection. The recovery, limit of detection (LOD) and limit of quantification (LOQ) of their proposed method were 68%, 20 ng/ml and 50 ng/ml, respectively. 5) An HPLC-MS method was developed for analyses of oseltamivir phosphate and oseltamivir carboxylate in plasma and urine samples with LOQs of 1 and 10 ng/ml for the prodrug and the active compound, respectively.6) A simple and rapid analysis of oseltamivir was reported using the HPLC-UV method in Tamiflu capsules. 8)Another HPLC-UV method was presented for the analysis of oseltamivir phosphate in Tamiflu ® capsules and two generic versions of the drug. 9) None of these latter methods 8,9) dealt with the possibility of separation of oseltamivir carboxylate. Lindegårdh et al.7) developed a solid-phase extraction and gradient HPLC coupled with a tandom mass spectrometer for analyses of oseltamivir phospha...

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Strategies for the investigation and control of process-related impurities in drug substances☆

Cited by 78 publications

References 66 publications

Normal phase and reverse phase HPLC-UV-MS analysis of process impurities for rapamycin analog ABT-578: Application to active pharmaceutical ingredient process development

Normal phase and reverse phase HPLC-UV-MS analysis of process impurities for rapamycin analog ABT-578: Application to active pharmaceutical ingredient process development

Impurity analysis of pharmaceuticals using capillary electromigration methods

Analysis of Oseltamivir in Tamiflu Capsules Using Micellar Electrokinetic Chromatography

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