A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops

Regulatory agencies focus on the N-nitroso Drug Substance Related Impurities (NDSRIs) for the safety and efficacy of the pharmaceuticals. This study highlights the control and detection of NDSRI impurity in the broad-spectrum antibiotic moxifloxacin (MOX). The objective of the present study is to de...

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Main Authors: Srinivas Nakka, Siva Krishna Muchakayala, Surendra Babu Manabolu Surya
Format: Article
Language:English
Published: Elsevier 2025-03-01
Series:Green Analytical Chemistry
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Online Access:http://www.sciencedirect.com/science/article/pii/S2772577424000971
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author Srinivas Nakka
Siva Krishna Muchakayala
Surendra Babu Manabolu Surya
author_facet Srinivas Nakka
Siva Krishna Muchakayala
Surendra Babu Manabolu Surya
author_sort Srinivas Nakka
collection DOAJ
description Regulatory agencies focus on the N-nitroso Drug Substance Related Impurities (NDSRIs) for the safety and efficacy of the pharmaceuticals. This study highlights the control and detection of NDSRI impurity in the broad-spectrum antibiotic moxifloxacin (MOX). The objective of the present study is to develop a highly sensitive, rapid, and novel LC-QqQ-MS/MS method for the simultaneous trace-level quantification of N-Nitroso Moxifloxacin (N-MOX) and di-Nitroso pyrrolopiperidine (DNPP) in MOX drug substance and drug products. According to the Carcinogenicity Potency Categorization Approach (CPCA), N-MOX and DNPP are classified into potency category 4, with an acceptable intake (AI) of 1500 ng/day. Chromatographic separation was achieved using a Waters Cortecs T3 C18 column (100 mm × 3.0 mm, 2.7 µm) with 0.1 % formic acid and acetonitrile as mobile phases in gradient elution mode at a flow rate of 0.3 mL/min. Triple quadrupole mass spectrometry with electrospray ionization (ESI) in multiple reaction monitoring (MRM) was used for quantification. The specific mass transitions are m/z 431.0 → 386.0 for N-MOX and 185.1 → 138.1 for DNPP. The developed method was successfully validated, and the results were within the acceptable range according to ICH guidelines. Moreover, we evaluated the eco-friendliness and greenness of the current method using enhanced tools. The results indicated a low environmental impact in terms of analysis time, solvent consumption, waste production, and sample quantity required. The method was successfully applied to quantify N-MOX in commercial MOX tablets and eye drops with a shorter run time; hence, it can quantify the presence of N-MOX and DNPP to ensure human safety and public health from using MOX formulation products.
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spelling doaj-art-dd8ecacc31f64d21ac4132273bb3c63b2025-08-20T01:56:20ZengElsevierGreen Analytical Chemistry2772-57742025-03-011210018810.1016/j.greeac.2024.100188A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye dropsSrinivas Nakka0Siva Krishna Muchakayala1Surendra Babu Manabolu Surya2Department of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, 502329, IndiaDepartment of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, 502329, India; Catalent Pharma Solutions, 1100 Enterprise Dr, Winchester, KY, 40391, USADepartment of Chemistry, School of Science, GITAM Deemed to be University, Hyderabad, 502329, India; Corresponding author at: Department of Chemistry, School of Science, GITAM Deemed to be University, India.Regulatory agencies focus on the N-nitroso Drug Substance Related Impurities (NDSRIs) for the safety and efficacy of the pharmaceuticals. This study highlights the control and detection of NDSRI impurity in the broad-spectrum antibiotic moxifloxacin (MOX). The objective of the present study is to develop a highly sensitive, rapid, and novel LC-QqQ-MS/MS method for the simultaneous trace-level quantification of N-Nitroso Moxifloxacin (N-MOX) and di-Nitroso pyrrolopiperidine (DNPP) in MOX drug substance and drug products. According to the Carcinogenicity Potency Categorization Approach (CPCA), N-MOX and DNPP are classified into potency category 4, with an acceptable intake (AI) of 1500 ng/day. Chromatographic separation was achieved using a Waters Cortecs T3 C18 column (100 mm × 3.0 mm, 2.7 µm) with 0.1 % formic acid and acetonitrile as mobile phases in gradient elution mode at a flow rate of 0.3 mL/min. Triple quadrupole mass spectrometry with electrospray ionization (ESI) in multiple reaction monitoring (MRM) was used for quantification. The specific mass transitions are m/z 431.0 → 386.0 for N-MOX and 185.1 → 138.1 for DNPP. The developed method was successfully validated, and the results were within the acceptable range according to ICH guidelines. Moreover, we evaluated the eco-friendliness and greenness of the current method using enhanced tools. The results indicated a low environmental impact in terms of analysis time, solvent consumption, waste production, and sample quantity required. The method was successfully applied to quantify N-MOX in commercial MOX tablets and eye drops with a shorter run time; hence, it can quantify the presence of N-MOX and DNPP to ensure human safety and public health from using MOX formulation products.http://www.sciencedirect.com/science/article/pii/S2772577424000971Di-Nitroso pyrrolopiperidineGreen chemistryMoxifloxacinMultiple reaction monitoringN-nitroso moxifloxacin
spellingShingle Srinivas Nakka
Siva Krishna Muchakayala
Surendra Babu Manabolu Surya
A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops
Green Analytical Chemistry
Di-Nitroso pyrrolopiperidine
Green chemistry
Moxifloxacin
Multiple reaction monitoring
N-nitroso moxifloxacin
title A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops
title_full A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops
title_fullStr A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops
title_full_unstemmed A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops
title_short A facile and eco-friendly simultaneous quantification LC-TQ-MS/MS approach for N-Nitroso Moxifloxacin and di-nitroso pyrrolopiperidine in Moxifloxacin tablets and eye drops
title_sort facile and eco friendly simultaneous quantification lc tq ms ms approach for n nitroso moxifloxacin and di nitroso pyrrolopiperidine in moxifloxacin tablets and eye drops
topic Di-Nitroso pyrrolopiperidine
Green chemistry
Moxifloxacin
Multiple reaction monitoring
N-nitroso moxifloxacin
url http://www.sciencedirect.com/science/article/pii/S2772577424000971
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