A Review: Analytical Methods of Antibiotic Drug Tigecycline
Jadhav Rajshri D*, Datar
P.A., Shete R.V.
Department Of Pharmaceutical
Quality Assurance
Rajgad Dayanpeeth’s College
of Pharmacy, Bhor - Pune, Maharashtra, India.
*Correspondence: rajshrijadhav829@gmail.com
DOI: https://doi.org/10.71431/IJRPAS.2025.4409
|
Article
Information
|
|
Abstract
|
|
Review Article
Received: 21/04/2025
Revised:
23/04/2025
Accepted: 25/04/2025
Published: 30/04/2025
Keywords
Tigecycline; Impurities;
Method
validation;
RP-HPLC
|
|
A rapid, accurate, simple, and
reproducible UV, HPLC, and stability-indicating spectroscopic method has been
developed for the quantitative estimation of Tigecycline in both bulk drug
and pharmaceutical dosage forms. A selective, precise, and
stability-indicating high-performance liquid chromatography (HPLC) method was
established and validated for analyzing Tigecycline in its pharmaceutical
formulation. The method was validated in accordance with ICH guidelines to
ensure its reliability. HPLC remains the most widely adopted technique for
separating, identifying, and quantifying pharmaceutical compounds. To
optimize the analytical method, several chromatographic parameters were
fine-tuned, including sample preparation, selection of mobile phase, choice
of column, and detection system. This paper aims to present a detailed
overview of the method development, optimization, and validation procedures.
|
INTRODUCTION
Tigecycline, chemically
named as( 4S, 4aS, 5aR, 12aR)- 9-(( 2-( tert- butylamino) acetyl) amino)
-4,7-bis( dimethylamino),- tetrahydrotetracene-2-carboxamide, is a broad-
diapason glycylcycline antibiotic structurally related to tetracycline. It's
biosynthesized by the Streptomyces
rubric of Actinobacteria and functions as a bacteriostatic agent. This
retailed under the brand name Tygacil, Tigecycline was approved by the U.S.
Food and Drug Administration( FDA) in 2005. According to the International
Council for Harmonisation( ICH), new pharmaceutical substances and their
lozenge forms must suffer stability
testing. Tigecycline has preliminarily
been anatomized using colorful ways, including spectrophotometry, fluorescence- grounded styles, and liquid chromatography coupled
with ultraviolet discovery( HPLC-UV). fresh
logical approaches similar as
stability- indicating styles have been
developed to assess Tigecycline in its parenteral lozenge form. A review of
being literature reveals a limited number of validated styles available for Tigecycline analysis
using UV-Visible spectrophotometry and rear- phase high- performance liquid
chromatography( RP- HPLC). While a many RP- HPLC, LC- MS/ MS, and HPTLC styles have been reported for the discovery
of Tigecycline in natural samples,these
remain fairly scarce. (1, 2 ,3) The current
exploration aims to develop and validate a simple rapid-fire, accurate,
and precise system for the analysis of
Tigecycline in both bulk and pharmaceutical
phrasings. As per ICH guidelines, stability- indicating logical styles
must be able of assessing the medicine’s
stability under stress conditions,
similar as hydrolysis, oxidation, photolysis, and thermal declination. According to FDA
recommendations, these styles should
allow for direct quantification of the active pharmaceutical component without hindrance from declination products, process contaminations.(7,8, 15)
Impurities: Tigecycline and its
impurities 1 and 2 are degraded. Which
are separated and characterized by NMR, HRMS and IR spectral investigation In
antimicrobial action Impurities, 1 and 2 shows good activity in the direction
Gram-negative and Gram-positive. 1
and 2 in bulk drug and formulations (16)
Structures:
Tigecycline
Impurity 1
Impurity 2
Force Degradation study:
Forced degradation
involves exposing a drug substance to extreme environmental and chemical
conditions to assess its stability profile. These studies help in understanding the molecule's
chemical behavior and provide valuable insights into potential degradation
pathways and products. This
information is crucial for identifying the structure of degradation products
and evaluating the drug's overall stability.There is a certain stabilities
acidic and basic hydrolysis, oxidation, heat, and light exposure. (16)
HPLC:
High-performance liquid chromatography (HPLC) . Its functions by separating,
identifying, and quantifying components in samples dissolved in liquid. The method depends on the
distribution of the analyte between a mobile phase (eluent) and a stationary
phase, typically within the column's packing material. HPLC plays a crucial role in pharmaceutical analysis,
valued for its high accuracy and reliability in both qualitative and
quantitative evaluations. (20)
Analytical Methods of Tigecycline:
|
Sr.no.
|
Methods
|
Tigecycline
|
Ref.
|
|
1.
|
RP - HPTLC
|
§
Column
: RP-18 Silica Gel 60 F25S
§ Mobile
Phase : Methanol:
Acetonitrile: Water (3: 3: 4 v/v/v)
§
Wavelength
: 245 nm
§
Rf value :
0.7 ± 0.02
§ Calibration
curve : 1000- 6000
ng//band
§
Limit of detection 0.7 ng/band
§
Limit of Quantification 2.328ng/band
§
Linearity 0.998
|
17
|
|
2.
|
RP-HPLC (Isocratic)
|
§ Column Agilent ZORBAX Eclipse XDB
C18 (250 mm × 4.6 mm, 5 μm)
§ Mobile Phase : methanol: 10 mmol Triethylamine Buffer mixture (75:25 v/v, pH 6.1)
§ flow rate 1 ml/min
§ wavelength, 231 nm
§ Linearity 75–450 μg/ml
§ LOD &LOQ 1.37,0.047 and 0.071 μg/ml
|
18
|
|
3.
|
UV
|
§
Wavelength
250 nm,
§
Range
2 to 12 μg/mL
§
R2 < 0.999
§
Precision 0.3269711
|
19
|
|
4.
|
UV
Spectroscopy
|
§ Wavelength 250nm
§ concentration range of 2-30μg/ ml
§ correlation coefficient (R2) 0.999
|
§
LOD
|
0.1527 μg/ml
|
|
§
LOQ
|
0.4635 μg/ml
|
|
13
|
|
5.
|
Stability indicating
|
§
Wavelength 250nm.
§
Column
C18 column (250 × 4.6 mm, 5μm)
§ Mobile
phase acetonitrile
and acetic acid (20:80).
§ Flow
rate 0.4ml/min
§ Retention
time 5.02 min
§ Range 50 – 150 μg/ml.
§ R2 0.999
|
15
|
|
6.
|
RP- HPLC
|
|
Column C18 column (Kromasil ODS C-18)
|
|
§ Mobile phase Buffer (1-Hexane
Sulphonic acid Sodium Monohydrate Salt and Potassium Dihydrogen Ortho
Phosphate)and Acetonitrile (83:17) v/v
|
§
flow rate 1.2 ml/min
§
Retention time 7.6 min.
§
Range 40-60 μg/ml
§
Correlation coefficient of 0.9999.
§
Recovery 100.92%.
§
LOD &LOQ 1.8μg/ml and
5.42μg/ml.
|
|
|
9
|
|
7.
|
RP-HPLC
|
Column Sunsil C18 150 mm x
4.6mm x 5μ
Mobile
phase
acetonitrile : water [70:30]
flow rate 0.8 ml/min
Wavelength
250 nm.
range of 5-40 μg/mL
|
20
|
|
8.
|
RP- LC
|
Column Luna C18 column
(250x4.6mm)
Mobile phase sodium phosphate
monobasic (0.015M) and oxalic acid(0.015M)- acetonitrile (75:25,v/v)
Flow rate 1.0 ml/min.
Wavwlength – 280nm
Range 40-100ug/ml
Accuracy 99.01%
LOD&LOQ 1.67 and 5.05 ug/ml
|
21
|
CONCLUSION
In this review paper provides this
information. . This includes HPTLC, UV, and LC methods;
among them, the HPLC-UV method remains a valuable analytical tool due to its
cost-effectiveness and reliability, making it particularly advantageous for
bioanalytical applications.
REFERENCE:
1.
Mr. Jay, J. Kelvin, and B. Pierre, Understanding and
Implementing Efficient Analytical Methods Development and Validation, 2003
2.
Ravisankar P, Rajyalakshmi G, Devadasu Ch, and Devala Rao G,
Instant tips for right and effective approach to solve HPLC trouble shooting,
Journal of chemical and pharmaceutical sciences, 2014; 7(3): 259-274.
3.
Jay Breaux, Kevin
Jones, and Pierre Boulas, Development services analytical method development
and validation Pharmaceutical technology, 2003; 27(1): 6-13.
4.
Matthew, Hutchings A,
Truman W, Barrie W. Antibiotics: Past, present and future. Current Opinion in
Microbiology 2019; 51: 72-80.
5.
Tilman
CS, Liege, Belgium. Gliptins, dipeptidyl peptidase-4 inhibitors, and risk of
acute pancreatitis. Pubmed 2013; 12(4): ): Biosci
Res. 2012; 2(2):88-91.
6.
Silva LM, Almeida AE, Salgado HR. Thermal analysis and validation
of UV and visible spectrophotometric methods for the determination of new
antibiotic Tigecycline in pharmaceutical product. Adv Anal Chem. 2012; 2:10-5.
7.
M .Akiful Haque, Sandeep Reddy, Gowri Manoja Mulagada,
Vasudha Bakshi Development and validation of RP-HPLC method for the estimation
of Tigecycline in bulk and its parenteral dosage form. MOL2NET, ICSM 2018
8.
Suneetha A, Priyanka GH, Sujitha J. Development and
Validation of Stability Indicating RP-HPLC Method for Estimation of Tigecycline in Bulk and its
Parenteral Dosage Forms. WJPPS. 2017;6(8):1096-107.
9.
Hua Xi, Wei Li. Determination of Tigecycline for injection with
HPLC. Anhui Medical and Pharmaceutical Journal. 2009; 9.
10.
Blessy MR, Patel RD, Prajapat PN, Agrawa YK. Development of forced
degradation and stability indicating studies of drugs: A review. J Pharm Anal.
2014; 4(3):159-65.
11.
Khagga Bhavyasri, Chejati Mounika, M Sumakanth Method Development, Validation and Forced
Degradation Studies for Determination of Tigecycline in Bulk and Pharmaceutical
Dosage Form using UV Spectroscopy Journal of Young Pharmacists, Vol 12, Issue
2(Suppl), Apr-Jun, 2020
12.
Hani
Mohammed Hafez , Sona Soliman Barghash, Marwa M. Soliman,Moustafa K. Soltan,
Mohamed Abd Elrahman, Noha Salah Katamesh Central composite design driven
optimization of sustainable stability indicating HPLC method for the
determination of Tigecycline and greenness assessment
F1000 Research 2023, 12:341 last updated: 18
AUG 2023
13.
Kurien
J, Jayasekhar P StabilityIndicating HPLC Determination of Tigecycine in
Pharmaceutical Dosage forms IJPRSV-2,
I-4, 2013 ISSN No: 2277 – 7873
14.
Sharavanan SPN, Venkatesan C.S, Sathiyanarayanan S, Kabilan S.
Potential Impurities of tigecycline: synthesis, isolation, characterization and
in vitro pharmacological evaluation. Curr Pharm Anal. 2020;16 (6):730-42. doi:
10.2174/ 1573412915666190225160030.
15. Aayesha Ansari, Rashid Ansari,
Mohammad Mojeeb Khan. Development and Validation of RP-HPTLC Method for
Determination of Tigecycline hydrochloride in Bulk and its Formulation International Journal of
Pharmaceutical Research and Applications Volume 9, Issue 4 July Aug 2024, pp:
1444-1449
16.
V. N. . Kishore, G. V. Ramana Simultaneous Determination Of
Tigecycline And Its Potential Impurities By A Stability-Indicating RP-HPLC -UV
Detection Technique Int J App Pharm, Vol 14, Issue 1, 2022, 75-82
17.
Kirtimaya
Mishra, A Dash, A Jabeen, S.Vegesna, S.K Sahoo, V Gupta, D Jena Chemometric
Assisted UV-Spectrophotometric Quantification of Tigecycline in Parenteral
Dosage Form IJDDT, Volume 13 Issue 3, July - September 2023
18.
RP-HPLC
Method Development and Validation for Determination of Tigecycline in Bulk and
Pharmaceutical Dosage Form RBVRR women's college of pharmacy, Barkatpura, Hyderabad, between june 2019 and july 2020. Lucélia Magalhães da Silva, Hérida
Regina Nunes Salgado, Validation of a Stability-Indicating RP-LC Method for the
Determination of Tigecycline in Lyophilized Powder Journal
of Chromatographic Science, Volume 51, Issue 2, February 2013,
Pages 192–199
19.
Rao BV, Sowjanya GN, Ajitha A, Rao Uma MV. A review on
stability- indicating HPLC method development, World journal of pharmacy and
pharmaceutical sciences, 2015; 4(8): 405-423.
20.
Dhirendra Kumar Mehta, Mahato Ashok Kumar, Koiri Sonali HPLC Method Development And Validation: A
Review Wjpmr, 2024, 10(1), 233-241
Vol 10, Issue 1, 2024