Investigation of critical factors for the resolution of SR695, a key impurity, from efavirenz in the reversed-phase assay of efavirenz dosage forms

Weissburg, Robert P; Montgomery, Eda Ross; Junnier, Lisa A; Segretario, James; Cook, Stacy C.; Hovsepian, Paul K

doi:10.1016/s0731-7085(01)00638-0

Cited by 9 publications

(6 citation statements)

References 4 publications

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“…Several HPLC methods are available in the literature for individual drugs and for a combination with other drugs for determination of TDF, FTC, and EFV, but no stability-indicting assay method (SIAM) has been reported. [12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27] Few RP-HPLC 28-29 methods are reported for estimation of FTC and TDF in pharmaceutical formulation. The literature survey revealed that there are a very few HPLC and spectroscopic methods available for the determination of Emtricitabine, Tenofovir disoproxil fumarate, Cobicistat, Elvitegravir in pure and combined dosage forms.…”

Section: -9mentioning

confidence: 99%

Development and Validation of Stability-Indicating HPLC-DAD Method for Simultaneous Determination of Emtricitabine, Elvetegravir, Cobicistat and Tenofovir in Their Tablet Dosage Forms.

Rao¹,

Dannana²

2016

IJPER

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A Simple, accurate, specific and rugged reverse phase liquid chromatographic method was developed for the simultaneous estimation of Emtricitabine, Elvetigravir, Cobicistat and Tenofovir in bulk and tablet dosage form. A reverse phase gradient program has been developed to separate the all four active ingredients. The mobile phase consisting of 0.05M Phosphate buffer pH 3.0 (adjusted with dilute phosphoric acid) and Acetonitrile in the ratio 95:5 from 0 min to 4 minutes, further increased the Acetonitrile ratio from 5 to 50 from 4 min to 10 minutes, on a reverse phase C 18 column (250x4.6mm, 5 µ) with a flow rate of 1.0 ml/min, monitored at 240nm. The mean retention times of Emtricitabine, Elvetigravir, Cobicistat and Tenofovir were found to be 1.5, 5.4, 6.6 and 7.5 min respectively. The proposed method was validated in terms of Linearity, Range, Accuracy, Precision, Specificity, Robustness and Ruggedness and the method was successfully applied for the estimation of Emtricitabine, Elvetigravir, Cobicistat and Tenofovir in combined tablet dosage form.

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Section: -9mentioning

confidence: 99%

Development and Validation of Stability-Indicating HPLC-DAD Method for Simultaneous Determination of Emtricitabine, Elvetegravir, Cobicistat and Tenofovir in Their Tablet Dosage Forms.

Rao¹,

Dannana²

2016

IJPER

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“…The 1 H NMR (200 MHz) and 13 C NMR (50 MHz) spectra were recorded on a DPX 200 NMR spectrometer (Bruker Biospin GmbH, Rheinstetten, Germany). Aliquots of quinoline and amino alcohol were dissolved in deuterated chloroform (CDCl 3 ).…”

Section: Characterization Of Degradation Productsmentioning

confidence: 99%

“…The column temperature of the chromatographic method used was changed to 30 • C instead 40 • C to improve the separation of efavirenz and a critical impurity as previously described by a study of the same research group from Montgomery et al [13]. This impurity (IV) differs from efavirenz in that it contains a trans-alkene bond while efavirenz contains a triple bond.…”

Section: Quantitation Of Related Compounds In Efavirenz Drug Substancmentioning

confidence: 99%

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Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis

Ribeiro

Campos

Alves

et al. 2007

Journal of Pharmaceutical and Biomedical Analysis

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“…Literature survey revealed that there are analytical methods available for the determination of efavirenz from biological matrices [ 4 , 5 , 6 , 7 ], and few methods reporting efavirenz impurity analysis have been described in the literature [ 8 , 9 , 10 , 11 , 12 ] and pharmacopeia [ 13 , 14 , 15 ]. The reported methods were not suitable for the desired low level (<1.5 µg/day) quantification of the AMCOL impurity for a risk assessment and comparison with the impurity levels of the commercially available innovator product (brand name: Sustiva).…”

Section: Introductionmentioning

confidence: 99%

Trace Level Quantification of the (−)2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol Genotoxic Impurity in Efavirenz Drug Substance and Drug Product Using LC–MS/MS

et al. 2015

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Efavirenz is a non-nucleoside reverse transcriptase inhibitor used in the treatment of human immunodeficiency virus type-1 (HIV). (2S)-(2-Amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol (AMCOL), used as an intermediate in the synthesis of efavirenz and a degradation impurity, has an aminoaryl derivative which is a well-known alerting function for genotoxic activity. Upon request from a regulatory agency, a selective and sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) method was developed for trace level quantitative determination of AMCOL related compound of efavirenz, for a risk assessment and comparison of impurity levels with the commercially available innovator product (brand name: Sustiva). The method provided excellent sensitivity at a typical target analyte level of <2.5 ppm, an established threshold of toxicological concern (TTC), when the drug substance and drug product samples were prepared at 15.0 mg/mL. The AMCOL sample was analyzed on a Luna C18 (2) (100 mm × 4.6 mm, 3 µm) column interfaced with a triple quadrupole tandem mass spectrometer operated in a multiple reaction monitoring (MRM) mode. Positive electrospray ionization (ESI) was employed as the ionization source and the mobile phase used was 5.0 mM ammonium acetate-methanol (35:65, v/v). The calibration curve showed good linearity over the concentration range of 0.2–5.0 ppm with a correlation coefficient of >0.999. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 0.07 and 0.2 ppm, respectively. The developed method was validated as per international council on harmonization (ICH) guidelines in terms of LOD, LOQ, linearity, precision, accuracy, specificity, and robustness.

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Investigation of critical factors for the resolution of SR695, a key impurity, from efavirenz in the reversed-phase assay of efavirenz dosage forms

Cited by 9 publications

References 4 publications

Development and Validation of Stability-Indicating HPLC-DAD Method for Simultaneous Determination of Emtricitabine, Elvetegravir, Cobicistat and Tenofovir in Their Tablet Dosage Forms.

Development and Validation of Stability-Indicating HPLC-DAD Method for Simultaneous Determination of Emtricitabine, Elvetegravir, Cobicistat and Tenofovir in Their Tablet Dosage Forms.

Efavirenz related compounds preparation by hydrolysis procedure: Setting reference standards for chromatographic purity analysis

Trace Level Quantification of the (−)2-(2-amino-5-chlorophenyl)-4-cyclopropyl-1,1,1-trifluoro-3-butyn-2-ol Genotoxic Impurity in Efavirenz Drug Substance and Drug Product Using LC–MS/MS

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