Development of an HPLC Assay Method for Lenalidomide

Saravanan, G.; Rao, B.M.; Ravikumar, Muttineni; Suryanarayana, M.; Someswararao, N.; Acharyulu, Palle V. R.

doi:10.1365/s10337-007-0290-y

Cited by 12 publications

(10 citation statements)

References 6 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous reports of lenalidomide quantitative assays suggested acidic mobile phases for isocratic separation through a C-18 matrix [14,17]. Due to tailing issues with flavopiridol [18,19], we evaluated rapid gradient conditions and ammonium formate modifiers.…”

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Highly Sensitive Liquid Chromatography/Mass Spectrometry Method for Simultaneous Quantification of Lenalidomide and Flavopiridol in Human Plasma

Liu¹,

Farley²,

Johnson³

et al. 2008

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

Lenalidomide, an immunomodulatory agent, and flavopiridol, a broad cyclin-dependent kinase inhibitor, are both active therapies for clinical use in genomic high risk chronic lymphocytic leukemia (CLL). A high-performance liquid chromatographic assay with tandem mass spectrometric detection has been developed to simultaneously quantify lenalidomide and flavopiridol in human and mouse plasma to facilitate their combined clinical development. Samples were prepared by liquid-liquid extraction with acetonitrile- (ACN) containing internal standard (IS), genistein, followed by evaporation of solvent and reconstitution in 95/5 H2O/ACN. Lenalidomide and IS were separated by reverse phase liquid chromatography on a C-18 column using a gradient of H2O and ACN, each with 0.1% formic acid. Atmospheric pressure chemical ionization (APCI) in positive-ion mode with single reaction monitoring on a triple quadrupole mass spectrometer were applied to detect transitions of lenalidomide (260.06 > 149.10) and flavopiridol (402.09 > 341.02). Lower limits of quantification (LLOQ) of lenalidomide and flavopiridol were 1nM and 0.3nM respectively. Recoveries of lenalidomide and flavopiridol from human plasma ranged from 99% to 116% throughout their linear ranges. Within and between-run precision and accuracy of replicate samples were all less than 15%. This is the most sensitive analytical method reported to date for both lenalidomide and flavopiridol. This sensitivity will enable late terminal phase concentration measurements and accurate pharmacokinetic parameter estimation in a planned clinical trial with lenalidomide and flavopiridol in CLL patients.

show abstract

Section: Resultsmentioning

confidence: 99%

Development and Validation of a Highly Sensitive Liquid Chromatography/Mass Spectrometry Method for Simultaneous Quantification of Lenalidomide and Flavopiridol in Human Plasma

Liu¹,

Farley²,

Johnson³

et al. 2008

Therapeutic Drug Monitoring

View full text Add to dashboard Cite

show abstract

“…Though, there have been various methods available for LEN estimation, so far, to the best of our knowledge, there has not been any green method which involves combined application of GAC and QbD. [12][13][14][15] Most of these methods used ACN for method development which is not considered to be an environmentally favourable solvent or having complex mobile phase with high EAT scores. The present manuscript describes the involvement of two concepts GAC and QbD in method development and validation taking LEN as a model drug.…”

Section: Introductionmentioning

confidence: 99%

Development and Validation of an Environmentally Benign and Robust Stability Indicating Assay Method for Lenalidomide: Comprehensive Degradation Kinetics Study and Application of Synergistic Approach Involving Green Analytical Chemistry and Quality by Des

Saxena¹,

Saroj²,

Shah³

et al. 2019

IJPER

View full text Add to dashboard Cite

Objective: A state of the art, robust and environmentally benign stability indicating assay method (SIAM) has been developed for model drug Lenalidomide (LEN). Methods: A Green metrics assessment was conducted by environment assessment tool (EAT), analytical method volume intensity (AMVI) and Ecosolvent ® tool. Successful chromatographic separation was accomplished on a Thermo C18 GAC column having dimensions of 4.6×150 mm and 3µ particle size using green solvents viz., methanol and acetate buffer in the ratio of 85:15. Results: The obtained EAT score and AMVI were 32.19 and 24 mL respectively. A green SIAM was developed and it was validated as per ICH Q2 (R1) guidelines. Quality by Design (QbD) approach was incorporated at validation stage to prove the robustness of the developed green method by applying 2^5-2 Res III 2-level fractional factorial design (FFD). Conclusion: An extensive stress degradation study along with degradation kinetics were performed and probable degradation pathways were predicted.

show abstract

“…Sastry et al (18) reported two spectrophotometric methods for the quantitation of LDM in its pharmaceutical formulations, but these methods did not measure stability. A reversed-phase liquid chromatographic method with UV detection was developed for determination of LDM in the presence of process-related impurities in capsules (19). Reddy et al (20) developed an HPLC method for determination of LDM and its related substances.…”

Section: Introductionmentioning

confidence: 99%

A Validated Stability-Indicating and Stereoselective HPLC Method for the Determination of Lenalidomide Enantiomers in Bulk Form and Capsules

Alzoman

2016

J Chromatogr Sci

View full text Add to dashboard Cite

A simple, rapid and stability-indicating chiral HPLC (CHR-HPLC) method was designed for the enantiomeric separation of lenalidomide (LDM) in the presence of its degradation products. LDM was exposed to different accelerated stress factors. The degradation products were well resolved from the pure drug enantiomers. Separation of the LDM enantiomers was achieved on a LUX 5U cellulose-2 chiral column (250 × 4.6 mm i.d.) with a mobile phase consisting of methanol : glacial acetic acid : triethyl amine (100 : 0.01 : 0.01, v/v/v) at a flow rate of 1.2 mL/min. The detection wavelength was 220 nm, and ornidazole was the internal standard. The chiral method was validated in terms of its specificity, linearity, range, precision and accuracy as well as solution stability, robustness, limit of detection and limit of quantification. The calibration curve was linear for concentrations ranging from 2 to 1,000 ng/mL (r= 0.9999) for both LDM enantiomers. The proposed method, which met International Conference on Harmonization/Food and Drug Administration regulatory requirements, was utilized successfully for the determination of LDM in bulk and in capsules with acceptable accuracy and precision; the label demand percentages were 100.09 ± 0.80 and 99.97 ± 0.93 for the S-(-) and R-(+)-LDM enantiomers, respectively. Based on these results, this method should have great value when applied to quality control and stability studies of LDM.

show abstract

Development of an HPLC Assay Method for Lenalidomide

Cited by 12 publications

References 6 publications

Development and Validation of a Highly Sensitive Liquid Chromatography/Mass Spectrometry Method for Simultaneous Quantification of Lenalidomide and Flavopiridol in Human Plasma

Development and Validation of a Highly Sensitive Liquid Chromatography/Mass Spectrometry Method for Simultaneous Quantification of Lenalidomide and Flavopiridol in Human Plasma

Development and Validation of an Environmentally Benign and Robust Stability Indicating Assay Method for Lenalidomide: Comprehensive Degradation Kinetics Study and Application of Synergistic Approach Involving Green Analytical Chemistry and Quality by Des

A Validated Stability-Indicating and Stereoselective HPLC Method for the Determination of Lenalidomide Enantiomers in Bulk Form and Capsules

Contact Info

Product

Resources

About