Development and validation of a selective, sensitive and stability indicating UPLC–MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance

Reddy, A. Vijaya Bhaskar; Yusop, Zulkifli; Aris, Azmi; Majid, Zaiton Abdul; Umar, Khalid; Talib, Juhaizah

doi:10.1016/j.jpba.2016.05.026

Cited by 13 publications

(3 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Accuracy indicates that the observed results of an analytical method is compatible with the true concentration of the analyte in the same sample under the same operating conditions and over a short interval of time. Precision and repeatability are suitable indicators of random errors [ 19 ]. Inter and intra-day study was carried out for the precision assessment.…”

Section: Methodsmentioning

confidence: 99%

Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran

et al. 2018

View full text Add to dashboard Cite

Background Nowadays with the growing popularity of herbal remedies across the world, large sections of population rely on herbal drug practitioners for their primary care. Therefore there is a need to ensure about the safety of herbal drugs and to detect adulteration with undeclared active pharmaceutical ingredients. Herbal drugs are used as first-line drug therapy in some instances. Unfortunately even if there are claims as to be natural, undeclared active pharmaceutical ingredients have been detected in these supplements. Objectives The purpose of the present study was to analyse herbal weight gain drugs collected from herb shops located in Tehran, Iran to detect hidden pharmaceutical ingredients using UHPLC and GC/MS instrumentations. Methods Sixty herbal drugs advertised as weight gain supplements were gathered from herb shops Tehran province, Iran. All samples were analysed from analytical toxicology point of view to detect undeclared active pharmaceutical ingredients. Method was validated for quantitative analysis of cyproheptadine and dexamethasone. Results Method validity parameters showed good results for quantitative analysis of pharmaceutical ingredients. Cyproheptadine, dexamethasone, sildenafil, tramadol, caffeine and acetaminophen were detected in herbal weight gain drugs. Analysed dosage forms contained cyproheptadine and dexamethasone in concentrations higher than therapeutic doses. Quantitative analysis of contaminated drugs showed that the content of pharmacologic ingredients were 0.2–67 and 5.5–10.1 mg/tablet or capsule for cyproheptadine and dexamethasone respectively. Conclusions Despite natural supplements producers’ claim, herbal weight gain drugs were not natural at all. Undeclared active pharmaceutical ingredients can predispose patients to health problems and even life-threatening situations. Graphical Abstract ᅟ

show abstract

Section: Methodsmentioning

confidence: 99%

Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran

et al. 2018

View full text Add to dashboard Cite

show abstract

“…For acidic functional groups that easily loose a proton, negative ionization mode can be applied. Several instruments can nowadays also switch polarity within several tens of milliseconds, making the simultaneous analysis of compounds ionized in different ionization polarity, possible [14][15][16] .…”

Section: Ionizationmentioning

confidence: 99%

Current developments in LC-MS for pharmaceutical analysis

Beccaria

Cabooter

2020

Analyst

164

View full text Add to dashboard Cite

show abstract

“…In accordance with the limit requirements of these impurities, an accurate, specifc, convenient HPLC method was established to determine impurities I-IV, and a highly sensitive and reliable HPLC-MS/MS method was developed successfully for the analysis of impurity V at a 30 ppm level due to the low sensitivity of the UV detector. Te proposed methods were validated in accordance with ICH guidelines [22][23][24][25][26], and the greenness assessment of two methods was evaluated by using AGREE software [27,28]. Te proposed HPLC method and the HPLC-MS/MS method represent favorable protocols in quality control and in-process monitoring during pharmaceutical manufacturing.…”

Section: Introductionmentioning

confidence: 99%

Identification and Determination of Impurities in a New Therapeutic Agent for Fatty Liver Disease

Shao

Feng

Zhang

et al. 2023

Journal of Analytical Methods in Chemistry

View full text Add to dashboard Cite

Methyl 7,7′-dimethoxy-5′-(morpholinomethyl)-[4,4′-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities I–IV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.1–2.0 μg/mL for impurities I–IV and 0.3–30.0 ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05 ng/mL and 0.005 μg/mL for impurity V and impurities I–IV, respectively. The precision and repeatability of the methods were less than 1.08% and 8.72% for each impurity. The recovery percentages of all impurities were in the range of 91.18%–111.27%, with the relative standard deviation of less than 3.69%. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results.

show abstract

Development and validation of a selective, sensitive and stability indicating UPLC–MS/MS method for rapid, simultaneous determination of six process related impurities in darunavir drug substance

Cited by 13 publications

References 21 publications

Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran

Determination of synthetic pharmaceutical adulterants in herbal weight gain supplements sold in herb shops, Tehran, Iran

Current developments in LC-MS for pharmaceutical analysis

Identification and Determination of Impurities in a New Therapeutic Agent for Fatty Liver Disease

Contact Info

Product

Resources

About