Research Journal of Pharmacy and Technology

Open Access Open Access  Restricted Access Subscription Access
Open Access Open Access Open Access  Restricted Access Restricted Access Subscription Access

Quantitative Determination of Trace Amounts of Diethylhexyl Phthalate Content in Dextrose Injection Proficiently by a Simplistic Gas Chromatography Technique


Affiliations
1 Research and Development Centre, Bharathiar University, Coimbatore - 641046, Tamilnadu,, India
2 Chemistry Research Laboratory, HMSIT, Tumkur, Karnataka, India
     

   Subscribe/Renew Journal


The objective of present study was to analyze Diethylhexyl phthalate content in 5% Dextrose injection and other reconstituting diluents for pharmaceutical injectable formulations. Reconstituting diluents for pharmaceutical injectable formulations are mainly stored and supplied in polyvinyl chloride bags. This may lead to leaching of Diethylhexyl phthalate, a toxic content from polyvinyl chloride bags into reconstituting formulations. In the current study, a proficient and simple method by using a Gas Chromatograph was developed and validated for the quantitation of trace amounts of Diethylhexyl phthalate in 5% Dextrose injection. The method was optimized by using silica fused short capillary column (DB-1; USP G2 phase) with dimensions 5 m length x 0.53 mm inner diameter and 2.65μm film thickness. The method involves a simple extraction procedure for sample preparation by means of extraction with n-Hexane solvent and evaporation with a stream of nitrogen gas. An Internal standard (1-Phenydodecane) was added to standard and sample preparations by using n-Hexane as diluent. The method was validated as per the current regulatory guidance for analytical method validation.The projected methodology was found to be selective, accurate, precise, and linear in the test concentration range from 0.004 μg/mL to 5.065μg/mL for Diethylhexyl phthalate. The method was effectively used to analyze the Diethylhexyl phthalate content in 5% Dextrose Injection and other reconstituting diluents for pharmaceutical injectable formulations.

Keywords

Diethylhexyl phthalate, 1-Phenyldodecane, Gas chromatography, 5% Dextrose injection, Reconstituting diluents.
Subscription Login to verify subscription
User
Notifications
Font Size


  • Toxicological Profile for Di(2-ethylhexyl) Phthalate, U.S. Department of Health and Human Services, Public Health Service, Agency for Toxic Substances and Disease Registry (1993).

  • European Commission, Health and Consumer Protection Directorate- General Opinion on medical devices containing di-(2-ethyl hexyl) phthalate plasticized PVC; Neonates and other groups possibly at risk for di-(2-ethyl hexyl) phthalate toxicity, The Scientific Committee on Medical Products and Medical Devices. 1 (2002).

  • United States Consumer Product Safety Commission, Test Method: CPSC-CH-C1001-09.3 Standard Operating Procedure for Determination of Phthalates, 2 (2010).

  • USFDA, Centre for devices and radiological health, Safety assessment of di-(2-ethylhexyl) phthalate released from PVC medical devices. 12, 1 (2014).

  • National Toxicology Programme, Centre for evaluation of risks to human reproduction, NIH Pub. 6, 1, (2006).

  • Safety Assessment of Di(2-ethylhexyl) phthalate (DEHP) Released from PVC Medical Devices-Center for Devices and Radiological Health U.S. Food and Drug Administration.3 (2015)

  • Di(2-ethylhexyl) phthalate-IARC Monograph.77, 2 (2000)

  • Preuss R, Koch HM, Angerer J Biological monitoring of the five major metabolites of di-(2-ethylhexyl) phthalate(DEHP) in human urine using column-switching liquid chromatography–tandem mass spectrometry. J. Chromatogr. B 816, 269 (2005).

  • Oishi S, Hirga K Distribution and elimination of di-2-ethylhexyl phthalate (DEHP) and mono-2-ethylhexyl phthalate (MEHP) after a single oral administration of DEHP in rats. Archives of Toxicology, 151, 149 (1982).

  • Silva MJ, Malek NA, Hodge CC, Reidy JA, Kato K, Barr DB, Needham LL, Brock JW. Improved quantitative detection of 11 urinary phthalate metabolites in humans using liquid chromatography–atmospheric pressure chemical ionization tandem mass spectrometry. J. Chromatogr. B 789, 393 (2003).

  • Lizak R, Verlinde P, Karasek L, Wenzl T Determination of bis-(2-ethylhexyl) phthalate (DEHP) in sports drinks by isotope dilution headspace solid phase micro extraction gas chromatography mass spectrometry (HS-SPME-GC-MS), Joint Research Centre – Institute for Reference Materials and Measurements, 11 (2011).

  • Sjoberg P, Bondesson U Determination of di(2-ethylhexyl) phthalate and four of its metabolites in blood plasma by gas chromatography–mass spectrometry. J. Chromatogr. B 344, 167 (1985).

  • Sircar D, Sargon J. Albazi, Atallah Y, Pizzi W Validation and Application of an HPLC Method for Determination of Di (2-ethylhexyl) Phthalate and Mono(2-ethylhexyl) Phthalate in Liver Samples. Journal of Chromatogr. Sci. 46, 627 (2008).

  • Chaudhary AK, Waske SA, Yadav S, Chandrashekhar TG, Singh V Validated Reverse Phase HPLC Method for the Determination of DEHP Content in Reconstituting Diluents and in Reconstituted Solutions of Imipenem and Cilastatin for Injection, E-Jour of Chem, 7, 501 (2010).

  • Eide M, DimethylPhthalate, Diethyl Phthalate, Dibutyl Phthalate, Di-2-ethylhexyl Phthalate, OSHA in-house file 3, (1989).

  • Atul Bajaj, Development and Validation of Gas Chromatography/Mass Spectrometry Method for the Simultaneous Determination of Some Preservatives in Personal Care, Cosmetics and Pharmaceutical Formulations; Research J. Science and Tech. 2017; 9(3): 308-312. DOI: 10.5958/2349-2988.2017.00055.9

  • Sathammai Priya1, Gas chromatography and mass spectroscopy analysis of phytoactive components on the seed extract of Caesalpinia bonducella; Research J. Pharm. and Tech. 2019; 12(10):4628-4634. DOI: 10.5958/0974-360X.2019.00796.0

  • Nagham Makhoul, Determination of Benzene in some Beverages under certain conditions; Research J. Pharm. and Tech 2019; 12(1): 37-39. DOI: 10.5958/0974-360X.2019.00007.6

  • Jenan Mohammed Ubaid, Bioactive Chemical Compounds Identified in Methanolic Extract of Trogoderma granarium; Research J. Pharm. and Tech 2017; 10(11): 3997-4004. DOI: 10.5958/0974-360X.2017.00725.9

  • Hussein J. Hussein, Using Gas Chromatography-Mass Spectrometry (GC-MS) Technique for Analysis of Bioactive Compounds of Methanolic Leaves extract of Lepidium sativum; Research J. Pharm. and Tech 2017; 10(11): 3981-3989. DOI: 10.5958/0974-360X.2017.00723.5

  • V. Bharathi1, Chemical Characterization from GC-MS Studies of Ethanolic Extract of Macrotyloma uniflorum; Research J. Pharm. and Tech. 9(3): Mar. 2016; Page 238-240 DOI: 10.5958/0974-360X.2016.00043.3

  • E. K. Okoro, Gas Chromatography-Mass Spectrometry determination of bioactive components in Annona muricata seed (soursop seed) methanol extract; Res. J. Pharmacognosy and Phytochem. 2016; 8(4): 231-234. DOI: 10.5958/0975-4385.2016.00034.0

  • Okoro Ebere Kelechi, Characterization of Annona muricata stem methanol extract by gas chromatography–mass spectrometry analysis; Res. J. Pharmacognosy and Phytochem. 2016; 8(3): 165-171. DOI: 10.5958/0975-4385.2016.00028.5

  • Patil Ankita Sanjeev, Chemical Constituents from Polyalthia longifolia seeds extract by Gas Chromatography-Mass Spectroscopy (GC-MS) Studies; Research J. Pharm. and Tech 2018; 11(6): 2489-2492. DOI: 10.5958/0974-360X.2018.00459.6

  • Rajabudeen E., GC-MS Analysis of the Methanol Extract of Tephrosia villosa (L.) Pers; Asian J. Research Chem. 5(11): Nov. 2012; Page 1331-1334

  • International Conference on Harmonization (ICH), Q2 (R1) Validation of Analytical Procedures: Text and Methodology (2005).

  • USP <1225>; Validation of Compendial Methods (2014)

  • National Association of Testing Authorities, Australia; Guidelines for the validation and verification of quantitative and qualitative test methods (2012)

  • World Health Organization WHO Technical Report Series, No. 937; Supplementary Guidelines on good manufacturing practices: validation. 4 (2006).

  • Center for Drug Evaluation and Research (CDER) Reviewer Guidance Validation of Chromatographic Methods (1994).

  • Guidance for Industry Analytical Procedures and Methods Validation Chemistry, Manufacturing, and Controls Documentation U.S. Department of Health and Human Services Food and Drug Administration (2000).


Abstract Views: 133

PDF Views: 0




  • Quantitative Determination of Trace Amounts of Diethylhexyl Phthalate Content in Dextrose Injection Proficiently by a Simplistic Gas Chromatography Technique

Abstract Views: 133  |  PDF Views: 0

Authors

H Ramakrishna Reddy
Research and Development Centre, Bharathiar University, Coimbatore - 641046, Tamilnadu,, India
S. R. Pratap
Chemistry Research Laboratory, HMSIT, Tumkur, Karnataka, India
N. Chandrasekhar
Research and Development Centre, Bharathiar University, Coimbatore - 641046, Tamilnadu,, India

Abstract


The objective of present study was to analyze Diethylhexyl phthalate content in 5% Dextrose injection and other reconstituting diluents for pharmaceutical injectable formulations. Reconstituting diluents for pharmaceutical injectable formulations are mainly stored and supplied in polyvinyl chloride bags. This may lead to leaching of Diethylhexyl phthalate, a toxic content from polyvinyl chloride bags into reconstituting formulations. In the current study, a proficient and simple method by using a Gas Chromatograph was developed and validated for the quantitation of trace amounts of Diethylhexyl phthalate in 5% Dextrose injection. The method was optimized by using silica fused short capillary column (DB-1; USP G2 phase) with dimensions 5 m length x 0.53 mm inner diameter and 2.65μm film thickness. The method involves a simple extraction procedure for sample preparation by means of extraction with n-Hexane solvent and evaporation with a stream of nitrogen gas. An Internal standard (1-Phenydodecane) was added to standard and sample preparations by using n-Hexane as diluent. The method was validated as per the current regulatory guidance for analytical method validation.The projected methodology was found to be selective, accurate, precise, and linear in the test concentration range from 0.004 μg/mL to 5.065μg/mL for Diethylhexyl phthalate. The method was effectively used to analyze the Diethylhexyl phthalate content in 5% Dextrose Injection and other reconstituting diluents for pharmaceutical injectable formulations.

Keywords


Diethylhexyl phthalate, 1-Phenyldodecane, Gas chromatography, 5% Dextrose injection, Reconstituting diluents.

References