LC–MS/MS studies of ritonavir and its forced degradation products

Rao, R. Nageswara; Ramachandra, Bondigalla; Vali, R. Mastan; Raju, S. Satyanarayana

doi:10.1016/j.jpba.2010.06.004

Cited by 42 publications

(25 citation statements)

References 13 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This metabolite was described before in a biotransformation of ritonavir with a P450 of the strain Streptomyces platensis . Furthermore, products with the m/z ratio of 606.3 and 622.3 could be identified which were described as degradation products of ritonavir before and were also present in the sample directly taken after substrate addition . These products were excluded from the product profile.…”

Section: Resultsmentioning

confidence: 93%

Accessing the Biocatalytic Potential for C−H‐Activation by Targeted Genome Mining and Screening

et al. 2019

View full text Add to dashboard Cite

Cytochrome P450 monooxygenases (P450s) are ubiquitous hemeproteins that insert oxygen specifically into substrates leading to diverse chemical transformations. Utilizing their capabilities, microbial whole-cell biocatalysts are applied in pharmaceutical and fine chemical industry to produce biomolecules and drug metabolites. In order to synthesize novel bioactive compounds there is a great demand to identify P450s with new reaction and substrate scope. In this study, genome mining and an activity screening were successfully combined to discover so far underutilized biocatalysts. The screening revealed the expected broad range of reactions, such as hydroxylations, dealkylations, reductions and desaturations. For Actinosynnema mirum and ritonavir the biotransformation was transferred to a preparative scale resulting in a ritonavir conversion of 90 % after 48 h and 13 different metabolites analyzed by LC-MS 2 and NMR. These results clearly demonstrate the potential of the underlying approach to identify promising whole cell biocatalysts with good conversion and product scopes.[a] L. . Bacterial and fungal strains selected for activity screening. Shown are total numbers of found P450 sequences for CYPED (black) and PROSITE (green) and the number of homologous families (brown) and superfamilies (red). A: bacterial strains 1 Bradyrhizobium elkanii, 2 Cystobacter fuscus DSM 2262, 3

show abstract

Section: Resultsmentioning

confidence: 93%

Accessing the Biocatalytic Potential for C−H‐Activation by Targeted Genome Mining and Screening

et al. 2019

View full text Add to dashboard Cite

show abstract

“…For the reasons described above, anionic polymers were prioritized for the development of an amorphous RTV dispersion. A critical challenge to producing an acceptable amorphous dispersion of RTV in an anionic carrier by thermal processing is that the polymers are acidic and RTV is sensitive to both heat and acid, with the combination of the two resulting in rapid degradation of the drug [36]. For this reason, the KinetiSol technology was utilized to produce the amorphous RTV dispersions because the process has been shown to minimize degradation of compounds that are heat‐ and acid‐sensitive [37–39]…”

Section: Resultsmentioning

confidence: 99%

Bioavailability enhancement of a BCS IV compound via an amorphous combination product containing ritonavir

Miller¹,

Keen²,

Brough

et al. 2015

Journal of Pharmacy and Pharmacology

View full text Add to dashboard Cite

Oral absorption of AKBA is substantially limited by intestinal CYP3A activity and poor aqueous solubility. Consequently, AKBA's oral bioavailability is maximized by administration from a supersaturating formulation in conjunction with a CYP3A inhibitor. The AKBA-RTV combination tablet presented herein represents a breakthrough in the oral delivery of the compound facilitating future use as a drug therapy for broad spectrum cancer treatment.

show abstract

“…tablets formulation. The stability study of ritonavir was done by LC -MS, [12,13] so a simple method was developed by spectrophotometry study to do a cost effective stability study.…”

Section: Resultsmentioning

confidence: 99%

“…As Ritonavir is temperature sensitive, and the stability study was reported in soft gelatine capsule dosage form by liquid chromatography, [12] and in standard drug by Liquid chromatography -Mass Spectroscopy (LC-MS), [13] a simple stability study was developed by applying the same degradation conditions to the tablet dosage form as in case of the previously explained procedure for standard drug.…”

Section: Application Of Stress Degradation Study To Formulationmentioning

confidence: 99%

Method development, validation and stability study of ritonavir in bulk and pharmaceutical dosage form by spectrophotometric method

et al. 2011

View full text Add to dashboard Cite

Background: Ritonavir is a protease inhibitor and mostly used as a booster for increasing the bioavailability of other protease inhibitors like Atazanavir Sulfate and Lopinavir. Aims: Quality assessment of the new dosage form of Ritonavir i.e. tablets is very essential, so two sensitive, simple and precise methods are developed for quantification of Ritonavir in bulk and tablet dosage forms. Materials and Methods: The first method is based on first order derivative method and the second is based on area under curve method. Both the methods are validated according to international conference of harmonization (ICH) guidelines. A stability study of Ritonavir is done in UV -Visible Spectrophotometer under different stress conditions recommended by ICH guidelines. Results:The absorption maximum is found to be 239nm in methanol. The absorption maximum in first method is chosen at 253.2nm, and the linearity is found between 4 -20 µg/ml with coefficient of correlation value 0.9981. In the second method, the range for area under curve selected is 237 -242nm. The linearity is found between 4 -20 µg/ml with coefficient of correlation value 0.9992. Conclusion: The developed methods are validated and found to be simple, rapid, precise and cost-effective. The degradation study in tablet dosage form can be used as a stability indicating assay method.

show abstract

LC–MS/MS studies of ritonavir and its forced degradation products

Cited by 42 publications

References 13 publications

Accessing the Biocatalytic Potential for C−H‐Activation by Targeted Genome Mining and Screening

Accessing the Biocatalytic Potential for C−H‐Activation by Targeted Genome Mining and Screening

Bioavailability enhancement of a BCS IV compound via an amorphous combination product containing ritonavir

Method development, validation and stability study of ritonavir in bulk and pharmaceutical dosage form by spectrophotometric method

Contact Info

Product

Resources

About