A Selective and Sensitive Method Development and Validation by Lc–ms/MS Approach for Trace Level Quantification of Three Potential Genotoxic Impurities in Pantoprazole Sodium Drug Substance

doi:10.7324/rjc.2017.1041863

Cited by 3 publications

(4 citation statements)

References 7 publications

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“…In a 2017 publication on the analysis of potentially genotoxic impurities in pantoprazole sodium drug substance, Subbaiah et al listed the substance N -(4-hydroxyphenyl)acetamide as GTI-A. In fact, GTI-A is paracetamol (4′-hydroxyacetanilide), which is the most commonly used analgesic and antipyretic worldwide.…”

Section: Commentary On Publications Involving “Genotoxic Impurities”mentioning

confidence: 99%

“…A PDE value of 7.1 mg (Table 6) was determined for acetamide by Bercu et al 8 on the basis of ICH M7(R1) criteria for a nonmutagenic carcinogen. Given the magnitude of the PDE, 4733 times higher than the default lifetime TTC value of 1.5 μg/day, there is no clear rationale for developing a highly sensitive assay of the type described by Rajana et al 92 In a 2017 publication on the analysis of potentially genotoxic impurities in pantoprazole sodium drug substance, Subbaiah et al 93 listed the substance N-(4-hydroxyphenyl)acetamide as GTI-A. In fact, GTI-A is paracetamol (4′-hydroxyacetanilide), which is the most commonly used analgesic and antipyretic worldwide.…”

Section: N-oxidesmentioning

confidence: 99%

See 1 more Smart Citation

A Primer for Pharmaceutical Process Development Chemists and Analysts in Relation to Impurities Perceived to Be Mutagenic or “Genotoxic”

Snodin¹

2020

Org. Process Res. Dev.

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Regulatory guidance on impurities is becoming increasingly comprehensive and complex. The advent of ICH M7(R1) on mutagenic impurities has introduced a significant and sophisticated toxicological component that can easily be underestimated by the unwary. The term "genotoxic impurity" was used in guidelines that predated the current guidance but is now outdated, although it is still often (mis)used in publications on impurities. ICH M7(R1) applies only to mutagenic impurities, which are defined as compounds that are DNA-reactive and test positive in a bacterial reverse mutation assay or are predicted to do so using appropriate in silico structure−activity software. A tentative indication of mutagenic activity is provided by so-called structural alerts, which are certain electrophilic moieties within a chemical structure. It is now well-established that many conventional alerts are associated with a significant number of false-positive predictions of mutagenic potential. Consequently, caution is required when an alert is used to tag a particular impurity as "genotoxic" with no further checks. Such an approach might lead to the development of unnecessarily sensitive impurity assays, which may or may not be a deliberate choice, and possibly to wasted additional process development costs. This review is intended to provide pragmatic guidance on the evaluation of the mutagenicity status of impurities, on the basis of which it is possible to determine appropriate limits. In addition, a series of published examples are reviewed where analytical method development has been compromised by mistakes concerning mutagenicity status and where incorrect mechanistic assumptions have been made regarding the potential for the formation of particular impurities.

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Section: Commentary On Publications Involving “Genotoxic Impurities”mentioning

confidence: 99%

Section: N-oxidesmentioning

confidence: 99%

A Primer for Pharmaceutical Process Development Chemists and Analysts in Relation to Impurities Perceived to Be Mutagenic or “Genotoxic”

Snodin¹

2020

Org. Process Res. Dev.

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“…Data acquisition, analysis, and reporting were performed by analyst chromatography software. [13][14][15] Reagents and Chemicals A pharmaceutically pure sample of barnidipine reference standard was obtained from clear synthetics, Hyderabad as gift samples along with their analytical reports. HPLC grade methanol, acetonitrile, diethyl ether and ammonium acetate was obtained from Merck chemical division, Mumbai.…”

Section: Experimental Instrumentationmentioning

confidence: 99%

Simultaneous Estimation and Validation of Lc-MS Method for the Determination of Barnidipine in Human Plasma: Its Stability Indicating

Talari¹,

Kumar²

2019

RJC

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Various LC-MS/MS and RP-HPLC methods are reported in the literature for the estimation of barnidipine individually. According to the literature survey, there is no regulatory method reported for the estimation of barnidipine by LC-MS/MS in human plasma either in literature and pharmacopeia. Hence, in this study a Novel LC/MS/MS method was optimized and validated for simultaneous estimation and validation of barnidipine in human plasma in accordance with the USFDA, EMEA and other relevant regulatory guidelines. Bamidipine is an anti-hypertensive drug belonging to the dihydropyridine (DHP) group of calcium antagonists. It is available in a modified-release formulation which has a gradual onset of action and is effective in a single daily oral dose of 10 to 20 mg. Bamidipine has selective action against cardiovascular calcium antagonist receptors and its anti-hypertensive action is related to the reduction of peripheral vascular resistance secondary to its vasodilatory action. The clinical anti-hypertensive efficacy of barnidipine is similar to that of other DHP calcium antagonists such as nitrendipine and amlodipine, and anti-hypertensives belonging to other drug classes such as atenolol and enalapril. Barnidipine has been found to be as efficacious and well tolerated as hydrochlorothiazide in the management of hypertension in elderly patients. Barnidipine is generally well tolerated. As with other DHP calcium antagonists, vasodilator adverse events such as a headache, flushing and peripheral oedema account for most of the adverse events reported with its use and are usually transient. Oedema is less frequent than with amlodipine and nitrendipine. Its use is not associated with reflex tachycardia. The validated regulatory bioanalytical method for estimation of barnidipine by LC-MS/MS in human plasma is useful for analysis of subject samples to support generic ANDA applications for different regulatory authorities for introducing new generic drugs in affordable rates for the patients. Also the validated regulatory method would be used as supporting literature for developing and validating better method in CROs and clinical research organizations to support new generic drugs.

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“…There are many articles published by using LC/MS/MS technique. [5][6][7] Usually, the term genotoxicity used in studies of in-vivo and in-vitro to find the genetic modification in genes by using a different mechanism.…”

Section: Introductionmentioning

confidence: 99%

Systematic Lc-MS/MS Method for Quantification of 2,3-Dimethyl-2h-Indazole-6-Amine Content in Pazopanib Hydrochloride

Viswanath¹,

Reddy²,

Nagaraju³

2020

RJC

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A sensitive and rugged method was developed and validated by using liquid chromatography coupled with triple quadrupole spectrometer (LC/MS/MS) technique for the determination of 2,3-dimethyl-2H-indazole-6-amine content in pazopanib hydrochloride. The separation was achieved by using Hypersil BDS C18 15 cm *4.6 mm length and 5.0 µm width column. Mobile phase-A was 0.1% formic acid in water and mobile phase-B was acetonitrile in the ratio of 45:55 v/v with 1.0 mL/min flow rate in isocratic mode. The limit of detection (LOD) and limit of quantification (LOQ) signal to noise ratio values were obtained as 3.7 and 10.9 respectively. The linearity range between 0.6 to 6.0 ng/mL and the correlation coefficient was found 0.999. The recovery found between 98.8 to 101.3% at four different levels.

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A Selective and Sensitive Method Development and Validation by Lc–ms/MS Approach for Trace Level Quantification of Three Potential Genotoxic Impurities in Pantoprazole Sodium Drug Substance

Cited by 3 publications

References 7 publications

A Primer for Pharmaceutical Process Development Chemists and Analysts in Relation to Impurities Perceived to Be Mutagenic or “Genotoxic”

A Primer for Pharmaceutical Process Development Chemists and Analysts in Relation to Impurities Perceived to Be Mutagenic or “Genotoxic”

Simultaneous Estimation and Validation of Lc-MS Method for the Determination of Barnidipine in Human Plasma: Its Stability Indicating

Systematic Lc-MS/MS Method for Quantification of 2,3-Dimethyl-2h-Indazole-6-Amine Content in Pazopanib Hydrochloride

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