Determination of trace levels of hydrazine in the penultimate intermediate of a novel anti-infective agent

Jagota, Nirdosh K.; Chetram, Aneil J; Nair, Jay B.

doi:10.1016/s0731-7085(97)00053-8

Cited by 22 publications

(6 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to these considerations, serious concerns regarding the flammability of any vapors in the head space were raised. Therefore, the concentration of hydrazine in the distillate was monitored . The initial distillate collected in the heat up from 143 to 155 °C was found to contain ∼1 mg/mL hydrazine.…”

Section: Resultsmentioning

confidence: 99%

“…The water content (KF) was determined by Karl Fisher titration. Hydrazine concentrations were monitored as follows: hydrazine was eluted at room temperature from an Ion Pac CS 17 (4 × 250 mm) with 6 mM methane sulfonic acid using an electochemical detector, injection volume of 100 μL, flow rate 1.0 mL/min . Post column, 0.1 N NaOH was mixed with the stream for electrochemical detection.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

Kuethe¹,

Childers²,

Peng³

et al. 2009

Org. Process Res. Dev.

View full text Add to dashboard Cite

A safe and practical strategy has been developed for the largescale preparation of imidazole 7. The key transformation involved the Wolff-Kishner reduction of the sterically demanding neopentyl-trifluoromethylcyclopropyl imidazole ketone 8. The described process provided the desired product in 74% overall yield without recourse to chromatographic purification. Safety considerations which allowed for the reaction to be conducted safely on kilogram scale are discussed.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

Kuethe¹,

Childers²,

Peng³

et al. 2009

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…1 and other PG impurities PGI-A, PGI-C, PGI-D, PGI-E, PGI-F and PGI-G are likely possible from PGI-B and structures of these impurities are given in same scheme. There have been many reported methods used to detect and quantify hydrazine and hydrazone related impurities [6][7][8][9][10] and alkyl halides and molecular weight is 459.5. Apixaban is an anticoagulant and is routinely used in the treatment of stroke, embolism, infarct etc.…”

Section: Introductionmentioning

confidence: 99%

DEVELOPMENT AND VALIDATION OF SEVEN PHENYL HYDRAZINE CHLORO ESTER ISOMERS (PGIs) BY RP-HPLC-UV METHOD IN ANTICOAGULANT DRUG SUBSTANCE; APIXABAN

Ramana

Raja

Babu

et al. 2020

Int J Curr Pharm Sci

View full text Add to dashboard Cite

Objective: The objective of this work was to develop and validate a simple and sensitive reverse-phase high-pressure liquid chromatography method for the determination of seven potential genotoxic impurities in Apixaban drug substance. Methods: The optimized separation was achieved by using ACE 3 C18 PFP (150 mm×4.6 mm, 3 µm) HPLC column. The mobile phase-A was a degassed mixture of 0.01M Ammonium acetate buffer(PH adjusted 4.9±0.05 with diluted glacial acetic acid) and mobile phase-B was a degassed mixture of Acetonitrile, Isopropyl alcohol and Buffer PH 4.9 in the ratio of 60:20:20 v/v/v. The gradient program was operated at a flow rate of 1.0 ml/min and UV detection was at 330 nm. Results: The method was superior at linearity for seven impurities and correlation coefficient values were larger than 0.999, moreover, in the separation point of view, this method further achieved no matrix interference through chromatography by better resolution of the other impurities from the Apixaban drug substance and its related impurities for the accurate analysis of seven potential genotoxic impurities. The established limits of detection (LOD), limits of quantification (LOQ) values for the seven mutagenic impurities were each of 5 ppm (0.015µg/ml) and15 ppm (0.045µg/ml) respectively. The developed method was validated as per ICH guidelines and applied as a generic method to determine these seven potential genotoxic impurities for the pharmaceutical process control and drug material release. Conclusion: Validation of this analytical method was carried out including stability, selectivity, linearity, accuracy, system precision, method precision and intermediate precision thus proving that the described RP-HPLC method could be employed for fast and simple analysis of sevenphenyl hydrazine chloro ester isomers in Apixaban drug substance.

show abstract

“…In addition to this, some of these methods are more time consuming 21,23,24,33 with poor recovery records obtained from non-universal detectors such as the Electron Capture Detector 22 (ECD) and Nitrogen Phosphorous Detector 21,23 (NPD). There is a need for catalysts for such types of reactions with pre-concentration step requirement 25 and high temperature application 20,27 or extraction of derivatives with low boiling solvents is involved.…”

Section: Introductionmentioning

confidence: 99%

Single step derivatization with CF₃ enone of thiophene at ambient temperature to determine propellant grade hydrazines: a study by GC and GC-MS

Selvasekarapandian

Somanathan

Reddy

2015

Analyst

View full text Add to dashboard Cite

A simple, highly selective and rapid gas chromatography method (packed column with flame ionization detection) has been developed to determine hydrazine and monomethylhydrazine individually and for selective determination of hydrazine in the UH 25 mixture in organic medium. This method is based on the derivatization of hydrazine (at ambient temperature) with 1,1,1-trifluoro-4-(3-thienyl) (CF3 enone) in the absence of catalyst/buffer which leads to the formation of corresponding pyrazolidine/pyrazoline/pyrazole. The organic derivatives thus formed are then detected and their presence is confirmed by GC-MS. The GC method provides good resolution between CF3 enone and its derivatives with a total analysis time of 20 min. The concentration of CF3 enone and derivatization time are optimized to determine hydrazines in the concentration range of 0.4 mM to 0.2 M. The calibration curves based on peak areas of CF3 enone and its derivatives showed good linearity with r(2) ≈ 0.999 for the working range and the precision was found to be less than 1% for hydrazine, MMH and hydrazine in UH25. The recovery was found by the standard addition method. Under the established conditions, limits of detection were 20 μM for hydrazine, 10 μM for MMH and 20 μM for hydrazine in UH25. The tolerance limit for interfering amines was also found. The advantage of this method is the selective detection and determination of hydrazine in the UH25 mixture as 1,1-dimethylhydrazine present in UH25 cannot be derivatized with CF3 enone.

show abstract

Determination of trace levels of hydrazine in the penultimate intermediate of a novel anti-infective agent

Cited by 22 publications

References 15 publications

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

DEVELOPMENT AND VALIDATION OF SEVEN PHENYL HYDRAZINE CHLORO ESTER ISOMERS (PGIs) BY RP-HPLC-UV METHOD IN ANTICOAGULANT DRUG SUBSTANCE; APIXABAN

Single step derivatization with CF₃ enone of thiophene at ambient temperature to determine propellant grade hydrazines: a study by GC and GC-MS

Contact Info

Product

Resources

About

Determination of trace levels of hydrazine in the penultimate intermediate of a novel anti-infective agent

Cited by 22 publications

References 15 publications

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

A Practical, Kilogram-Scale Implementation of the Wolff−Kishner Reduction

DEVELOPMENT AND VALIDATION OF SEVEN PHENYL HYDRAZINE CHLORO ESTER ISOMERS (PGIs) BY RP-HPLC-UV METHOD IN ANTICOAGULANT DRUG SUBSTANCE; APIXABAN

Single step derivatization with CF3 enone of thiophene at ambient temperature to determine propellant grade hydrazines: a study by GC and GC-MS

Contact Info

Product

Resources

About

Single step derivatization with CF₃ enone of thiophene at ambient temperature to determine propellant grade hydrazines: a study by GC and GC-MS