STABILITY INDICATING REVERSE PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC METHOD FOR SIMULTANEOUS ESTIMATION OF LABETALOL AND ITS DEGRADATION PRODUCTS IN TABLET DOSAGE FORMS
DOI:
https://doi.org/10.22159/ajpcr.2016.v9s2.13687Abstract
ABSTRACT
Objective: The objective of the present work is to develop a simple, efficient, and reproducible stability indicating reverse phase high-performance
liquid chromatographic method for simultaneous determination labetalol and its degradation products in tablet dosage forms.
Methods: The chromatographic separation of labetalol and its degradation products in tablets was carried out on Zorbax Eclipse Plus C-18
(100 × 4.6 mm, 3.5 µm) column using 0.1% trifluoroacetic acid (TFA) (v/v) in 1000 ml of water and 0.1% TFA (v/v) in 1000 ml of acetonitrile:
Methanol (1:1) by linear gradient program. Flow rate was 1.0 mL min
with a column temperature of 35°C, and detection wavelength was carried out
at 230 nm. Known impurity is well resolved from the main active drug within 14 minutes run time.
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Results: The forced degradation studies were performed on labetalol tablets under acidic, basic, oxidation, thermal, humidity, and photolytic
conditions. No degradation products were observed from the forced degradation studies, and the known impurity is well resolved from the main
active drug. The method was validated in terms of specificity, linearity, limit of detection (LOD), limit of quantitation (LOQ), accuracy, precision, and
robustness as per the ICH guidelines. The method was found to be linear in the range of LOQ to 120% for all the known and unknown impurities.
The LOD and LOQ values of known impurity were found between 0.3593 and 0.7187 µg mL
, and the percentage recovery values were in the range
of 95.5-105.2% at different concentration levels. Relative standard deviation for precision and intermediate precision results were found to be <5%.
The correlation coefficient found for all compounds was not <0.99. The results obtained from the validation experiments prove that the developed
method is a stability indicating method.
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Conclusion: The developed method can be successfully applied for routine analysis, quality control analysis and also suitable for stability analysis of
the simultaneous determination of labetalol and its degradation products in tablet dosage forms as per the regulatory requirements.
Keywords: Labetalol, Development, Validation, Reverse phase high-performance liquid chromatography.
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References
REFERENCES
Available from: https://www.en.wikipedia.org/wiki/Labetalol.
Fahed S, Grum DF, Papadimos TJ. Labetalol infusion for refractory
hypertension causing severe hypotension and bradycardia: An issue of
patient safety. Patient Saf Surg 2008;2:13.
Louis WJ, McNeill JJ, Drummer OH. Labetalol and other vasodilator/
Beta-blocking drugs. In: Handbook of Hypertension. Amsterdam,
Netherlands: Elsevier Sciences Publishing Co.; 1988. p. 246-73.
Riva E, Mennini T, Latini R. The alpha- and beta-adrenoceptor
blocking activities of labetalol and its RR-SR (50:50) stereoisomers. Br
J Pharmacol 1991;104(4):823-8.
Robertson D, Biaggioni I. Adrenoceptor antagonist drugs. In:
Katzung BG, Masters SB, Trevor AJ, editors. Basic & Clinical
Pharmacology. 12
ed. San Francisco: McGraw-Hill Lange Medical;
p. 151-68.
th
hrs
Percentage
difference
standard solution
6 99.5 1.1
Percentage assay of
sample solution
Percentage 2-hydroxy
impurity
At refrigerated condition
Percentage assay of
2 99.3 0.9
154 0.148 0.01
standard solution
6 100.1 0.5
Percentage assay of
sample solution
Percentage 2-hydroxy
impurity
2 99.5 0.7
154 0.142 0.01
Koda Kimble MA, Alldredge BK. Koda Kimble and Young’s Applied
Therapeutic: The Clinical Use of Drugs. Philadelphia, PA: Lippincott
Williams & Wilkins; 2013.
MacCarthy EP, Bloomfield SS. Labetalol: A review of its pharmacology,
pharmacokinetics, clinical uses and adverse effects. Pharmacotherapy
;3(4):193-219.
Louis WJ, McNeil JJ, Drummer OH. Pharmacology of combined alphabeta-blockade.
I. Drugs 1984;28
Suppl
:16-34.
Bertram KG. Basic and Clinical Pharmacology. New York: McGrawHill
Medical; 2006. p.
Richards DA, Tuckman J, Prichard BN. Assessment of alpha- and
beta-adrenoceptor blocking actions of labetalol. Br J Clin Pharmacol
;3(5):849-55.
Xu QA, Timothy LM. Analytical Methods for Therapeutic Drug
Monitoring and Toxicology. Hoboken, NJ: John Wiley and Sons; 2011.
Available from: https://www.pubchem.ncbi.nlm.nih.gov/compound/
labetalol#section=Caco2-Permeability.
The United States Pharmacopoeia. USP-37, NF-32. Rochville, MD,
USA: United States Pharmacopeial Convention; 2014.
Jinqi Z, Lina FU, Chao L, Guogang Z. Determination of content and
related substances of labetalol hydrochloride by HPLC. Chin J Modern
Appl Pharm 2013;1:???.
Meredith PA, McSharry D, Elliott HL, Reid JL. The determination of
labetalol in plasma by highperformance liquid chromatography using
fluorescence detection. J Pharmacol Methods 1981;6(4):309-14.
Vaishali CK, Bhavika RC, Bavaskar SR, Barhate SD. Stability indicating
RP-HPLC method for determination of labetalol hydrochloride in
pharmaceutical formulation. World J Pharm Res 2015;4(4):1149-61.
Ganesan M, Nanjundan S, Rauthan KS, Eswaran K, Tripathi P.
AQ5
AQ2
AQ3
Asian J Pharm Clin Res, Vol 9, Suppl. 2, 2016, 242-249
Chakravarthy et al.
Rapid analysis of labetalol in human plasma using liquid
chromatography- tandem mass chromatography. Int J Pharm Sci Res
;1(12):209-18.
European Pharmacopoeia 8.0.
ICH. Q2 (R1), Harmonized Tripartite Guideline, Validation of
Analytical Procedures: Text and Methodology. In: Proceedings of the
International Conference on Harmonization of Technical Requirements
for Registration of Pharmaceuticals for Human Use; 2005.
Snyder LR, Kirkland JJ, Glajch JL. Handbook of Practical HPLC
Method Development. 2
ed. Hoboken, NJ, USA: Wiley-Blackwell;
nd
Basak AK, Raw AS, Al Hakim AH, Furness S, Samaan NI, Gill DS,
et al. Pharmaceutical impurities: Regulatory perspective for abbreviated
new drug applications. Adv Drug Deliv Rev 2007;59(1):64-72.
Bakshi M, Singh S. Development of validated stability-indicating assay
methods – critical review. J Pharm Biomed Anal 2002;28(6):1011-40.
United States Food and Drug Administration. Guidance for
Industry: Analytical Procedures and Methods Validation: Chemistry,
Manufacturing, and Controls Documentation. Draft Guidance.
Rockville, MD: USFDA; 2001.
Shabir GA. Validation of high-performance liquid chromatography
methods for pharmaceutical analysis. Understanding the differences
and similarities between validation requirements of the US Food and
Drug Administration, the US Pharmacopeia and the International
Conference on Harmonization. J Chromatogr A 2003;987(1-2):57-66.
Center for Drug Evaluation and Research (CDER). Reviewer Guidance:
Validation of Chromatographic Methods, CMC 3. USFDA; 1994.
Guidance for Industry, Analytical Procedures and Methods Validation
for Drugs and Biologics. Draft Guidance, U.S. Department of Health
and Human Services, Food and Drug Admin-Istration (FDA), Center
for Drug Evaluation and Research (CDER), Center for Biologics
Evaluation and Research (CBER), CMC; 2014.
Ravichandran V, Shalini S, Sundramand KM, Rajak H. Validation of
analytical methods-strategies & importance. Int J Pharm Pharm Sci
;2(3):18-22.
Pranshu T, Singh RP, Vikash J. Validation: A critical parameter for
quality control of pharmaceuticals. J Drug Deliv Ther 2012;2(3):34-40.
???. Validation of compendial methods. United States Pharmacopeia
, National Formulary 32. Ch. 1225.Rockville, MD, USA: The United
States Pharmacopeial Convention; 2014.
Ashok CV, Sailaja BB, Praveen KA. Development and validation of a
dissolution method for Frovatriptan tablets by reverse phase UPLC. Int
J Pharm Pharm Sci 2015;7(4):125-30.
Venkata RG, Pavani G, Supriya P, Madhavilatha N. Reverse phase
high performance liquid chromatography method development and
validation of atorvastatin in bulk drug and formulation. Asian J Pharm
Clin Res 2015;8(6):84-7.
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