A Review on Development of Analytical Methods for estimation of Quetiapine fumarate in Bulk and Pharmaceutical Formulation

 

Dolly Dewangan*, Jitendra Yadav, Kamraj, Krity Gupta, Manish Kumar Sahu, Parimal Verma, Prashant Kumar Sahu, Shweta Sinha, Aakanksha Sinha, S. J. Daharwal

University Institute of Pharmacy, Pt. Ravishankar Shukla University, Raipur (C.G).

*Corresponding Author E-mail: dollydewangan2543@gmail.com

A simple and accurate, rapid method had been developed for determination of Quetiapine fumarate in bulk and pharmaceutical dosage form. Quetiapine fumarate is a 2^nd generation a typical antipsychotic used for management of psychosis, Schizophrenia. The solvent, method, analytical procedure, reaction time, solvent concentration used are carefully optimised with maximum sensitivity. The proposed methods were successfully applied for the determination of QTF in pharmaceutical formulations.

 

 

INTRODUCTION:

A second-generation atypical antipsychotic drug Quetiapine fuamrate is approved by FDA in 1997 used for treatment for schizophrenia, major depression and bipolar disorder.¹ The Molecular formula of Quetiapine fumarate is (fumarate salt) C42H50N6O4S2.C4H4O4 and molecular weight is 883.092 g/mol. It described as 2-[2-(4-benzo[b] [1,4] benzothiazepin-6-ylpiperazin-1-yl) ethoxy] ethanol; (E)-but-2-enedioic acid.² An oral antipsychotic drug that acts as an antagonist of multiple neurotransmitters including serotonin and nor epinephrine is used in the treatment of schizophrenia. It is a selective monoaminergic antagonist with high affinity for the serotonin type 2 (5HT2) and dopamine type 2 (D2) receptors.³ The generic name of quetiapine hemifumarate is Seroquel.⁴

 

Physiochemical Properties:

It is white or almost white powder, moderately soluble in water and soluble in methanol and 0.1 N HCl.⁴ Quetiapine Fumarate is described chemically as 11- [4- [2-(2-Hydroxy ethoxy) ethyl]-1- piperazinyl] dibenzo (b, f) (1, 4) thiazepine hemifumarate.⁵. Its solid oral dosage form is available in tablet form as the fumarate salt. ⁶ The melting point is between 174-176°C.

 

Pharmacological Properties:

The drug is well absorbed by administration of oral route when reached to plasma concentration of 1 – 2 hour and the drug is 83% bound to serum protein. It have the half life of approximate 7 hours. The metabolism occur on liver involves pathway sulphoxidation with Cytochrome P450 and CYP3A4 isoenzyme. The half-life of Quetiapine is approximately 6 hours. After administration of Quetiapine, approximately 73% of the radioactivity was excreted in urine and 21% was excreted in feces. ⁷

Mechanism of Action:

Due to its antagonistic action at D2(dopamine) and 5HT2A (serotine) receptor. The mesolimbic and mesocortical are the areas of brain which are responsible for the pharmacological effect of antipsychotic drug.⁸

 

Requirement to Developed Analytical Method:

Analytical Chemistry involves detection, separation, identification, characterization of one or more compounds present in herbal and synthetic material. For determining the selectivity, specificity, limit of detection, limit of quantification, range, accuracy, precision, robustness there are several methods are developed for routine chemical analysis.⁹

 

Analytical method developed by UV visible spectrophotometer:

UV – Visible Spectrophotometer is most widely used instrument for identification of compound by absorbance of ultra violet and visible radiation. It has great role in drug development and drug discovery. It works on principle of Beer’s lambert law.¹⁰. Its non-destructive characteristics and elevated sensitivity render it an essential instrument for quality control, maintaining the uniformity and efficacy of pharmaceutical products. (Table-1 and 2).

 

Analytical method development by HPLC:

HPLC is the most important analytical tool used for identification of compounds based on differential migration of samples on between stationary phase and mobile phase. The molecules of sample which have greater affinity for stationary phase as well as lesser affinity for mobile phase will travel slower and the compound which have lesser affinity for stationary phase as well as greater affinity for mobile phase will travel faster.²⁴. It have high sensitivity to analyze small amount of analyte on sample.²⁵ (Table-3).

 

Table:-1

 

 

UV visible spectrophotometry in which indicator is used as solvent

 

Table:-2

 

Table:-3

S. No	Sample	Mobile phase	Column	Wavelength	Flow rate	Retention time	Reference
1	Tablet	MeOH: water (80:20 v/v)	Greece C18 (250 × 4.6 mm, 5μm)	213 nm	0.9	3.3min	26
2	Tablet	MeOH: water (80:20 v/v)	Eclipse XDB C18	302 nm	1.0	3.12 min	27
3	Tablet	Phosphate buffer with KCl: MeOH: ACN (40:50:10 v/v)	ZORBAX Stablebond phenyl column (150 × 2.1 mm, 5 mm)	225 nm	0.25		28
4	Tablet	ACN: MeOH (90:10 v/v)	Eclipse Plus C18 (100 × 4.6 mm, 3.5 mm)	220 nm	0.8	5.9 min	29
5	Tablet	0.15% TEA with ACN: MeOH (80:20 v/v)	Zorbax C8 (100 × 4.6 mm, 3 μm	252 nm	1.2		30
6	Tablet	MeOH: ACN: phosphate buffer (19:40:41 v/v)	C18	220 nm	1.0	3.186 min	31
7	Tablet	MeOH: ACN water (67:16:17 v/v)	C18 (250 × 4.6 mm, 5 μm)	220 nm	1.0	5.35 min	32
8	Tablet	Phosphate buffer with hexane sulphonate: ACN (74.4:25.6 v/v)	C18 (250 × 4.6 mm, 5 μm	220 nm	1.0	3.485 min	33
9	Bulk	5 mm CH3CO2NH4: ACN (50:50 v/v)	X-bridge C18 (150 × 4.6 mm, 5 μm)	220 nm	1.0	13.80 min	34
10	Bulk	10 mm KH2PO4: MeOH: ACN (450:300:250 v/v)	Agilent XDB-C18 (50 × 4.6 mm, 1.8 μm)	225 nm	1.0	6 min	35

Analytical method developed by RP- HPLC method

On the basis of hydrophobicity, the separation of neutral molecules the chromatography method is mainly used Reverse Phase chromatography is the reverse method of normal phase chromatography. It involve polar stationary phase and non – polar mobile phase.³⁶. These apparently used for routine quality control study of research and formulation tests.³⁷ It commonly used for quantitative and qualitative analysis of molecules, substance, drug.³⁸  (Table-4).

 

Analytical method development by HPTLC:

High-performance thin-layer chromatography (HPTLC) is highly sophisticated utilized technique for the analysis of natural products. It is used for qualitative and quantitative analysis of natural products. HPTLC is modern form of TLC with improved separation efficiency and better detection limits.⁴⁷  (Table-5)

 

Analytical method developed by TLC

Thin Layer Chromatography is a simple chromatography method to separate the compounds but its separation efficiency is less. The closed vessel in which a layer of stationary phase is coated on plate is used for qualitative and quantitative analysis of components. (Table-6).

 

Analytical method development by LC-MS

The methods for estimation of Quetiapine fumarate has been discussed in table-7.

 

Table:-4

S. No	Sample	Mobile Phase	Column	Wavelength	Flow rate	Retention time	Reference
1	Tablet	Phosphate buffer pH 6.6: ACN: MeOH (45:40:15 v/v)	C18 (250 × 4.6 mm, 3 μm)	220 nm	1.0	17.14 min	39
2	Tablet	Buffer: ACN (65:35 v/v)	Zorbax ODS C18 (150 × 4.6 mm, 5.0 μm)	257 nm	0.6	8.960 min	40
3	Tablet	Phosphate buffer (pH 3): ACN: MeOH (50:40:10 v/v)	Phenomix Stainless Steel C18 (250 × 4.6 mm, 5 μm)	247 nm	0.8	4.69 min	41
4	Tablet	0.02%v/v HCOOH: MeOH (90:10 v/v)	Inertsil ODS (250 × 4.6 mm, 5μm)	220 nm	1.0	13.4 min	42
5	Tablet	Phosphate buffer with OPA: ACN (40:60 v/v)	C18Waters (75×4.6mm, 3.5μm)	291 nm	0.8	2.929 min	43
6	Tablet	ACN: phosphate buffer (5:95v/v)	Hypersil C18 (250×4.6mm,5μm)	210 nm	1.0	3.65 min	44
7	Tablet	KH2PO4: MeOH	Zodiac C18 (100×4.6mm,3μm)	252 nm	1.0	23.06 min	45
8	Tablet	MeOH: water (30:70v/v)	C18	359	1.0	5.27 min	46

.

Table:-5.

S. No	Sample	Mobile Phase	Chamber saturation time	Detection	Retention factor	Reference
1	Tablet	Toluene: MeOH (7:4v/v)	10	235 nm	0.61	48
2	Tablet	Toluene: Ethylacetate: Diethyl amine (5:3:2v/v)	30	291 nm	0.54	49
3	Tablet	MeOH: Toluene (4:3v/v)	30	235 nm	0.41	50
4	Tablet	Toluene: Ethyl acetate: MeOH (5.5:4.0:0.5v/v/v)	20	290 nm	0.03	51
5	Tablet	Toluene: 1,4-dioxane: Dimethylamine (5:8:2v/v)	15	225 nm	0.97	52
6	Bulk	MeOH: Butanol : Ethylacetate (2:1:1v/v)	30	220 nm	0.76	53
7	Bulk	Toluene: MeOH (8:2v/v)	30	254 nm	0.37	54

 

 

 

Table:-6.

S. No	Sample	Mobile Phase	Chamber saturation time	Detection	Retention factor	Reference
1	Tablet	Hexane: ACN: 25%ammonia solution (60:40:2v/v)	15	254 nm	0.63	55
2	Tablet	Ethylacetate: MeOH:  10% NH4OH (8.5:1:0.5v/v)	15	302 nm	0.54	56

 

Table:-7.

S. No	Matrix	Solvent	Column	Detection wavelength	Flow rate	Retention time	Reference
1	Tablet	ACN: NH4COOH (90:10v/v)	Sciencehome C18 column (250×4.6mm, 5μm)	240 nm	1.0		48
2	API	TEA with OPA: CAN: MeOH (60:32:8v/v)	Kinetex C18 (150×4.6mm, 5μm	225 nm	1.0	14.5 min	49

 

 

Bioanalytical Method Development:

Bioanalysis is play essential role in drug discovery and drug development. It involve detection and identification of analyte (metabolite, biomarker, drug) in biological sample.⁵⁷ Bioanalysis is the method used to determine the concentration of drugs, their metabolites and endogenous substances in the biological matrices such as blood, plasma, serum, cerebrospinal fluid, urine, and saliva.^{58, 59}  (Table-8).

 

Table:-8.

S. No	Method	Sample	Mobile Phase/Solvent	Column	Detection	Saturation time	Retention time	Reference
1	UV	Human Urine	Chloroform: acetate:  HCl	-	420 nm	-	-	60
2	HPLC	Plasma	ACN:0.02M phosphate buffer (50:50v/v)	Zorbax SB-Phenylcolumn (250×4.6mmi.d.,5μm)	254 nm	1.0	4.1 min	61
3	HPLC	Blood/ liver/ Bile	ACN: 0.1M NH4OH (20:80v/v)	C8ODS (150×2.1mm,5μm)	258 nm	0.4	9.1 min	62
4	HPLC	serum	MeOH: ACN: Distilled water (17.6:36.8:45.6v/v)	ODS-3C18 (150×4.6mm,5μm)	254 nm	1.0	-	63
5	HPLC	Plasma	MeOH: water (85:15v/v)	C18 (250×4.6mm,5μm)	254 nm	-	-	64
6	HPLC	serum	MeOH:20mm CH3CO2NH4 (99:1v/v)	C2 cartridge	257 nm	1.0	5	65
7	HPLC	Human Plasma	CH3CO2NH4: MeOH (21:79v/v)	C18 (150×4.6mm,5μm)	254 nm	0.8	-	66
8	RP-HPLC	Blood	ACN:MeOH: 0.025M phosphate buffer with TEA (40:30:30v/v)	C18 (150×4.6mm,5μm)	225 nm	1.2	3.8	67
9	RP-HPLC	Human Plasma	ACN: phosphate buffer (50:50v/v)	C18 (150×4.6mm,5μm)	292 nm	1.0	5.92	68
10	LC-MS/ MS	Microso- mal Matrix	CH3CO2NH4: ACN	Kinetex 2.6lmC18100A◦ (50×2.1mm)	-	0.2	-	39
11	LC-MS/ MS	Plasma	NH4COOH: MeOH (55:45v/v)	Sunfire C18 (50×2.1mm, 5μm)	-	0.3	2.12	70
12	LC-MS/ MS	Plasma	ACN: CH3CO2NH4: HCOOH	PhenomenexLuna C18 (150×2.0mm, 5μm)	-	0.3	1.82	71
13	LC-MS/ Ms	HumanPlasma	ACN:MeOH: CH3CO2NH4	Atlantisd C18 column (100×3.0mm, 3μm)	-	0.4	0.85	72
14	Fluorescence spectroscopy	Human plasma	4-chloro-7 nitrobenzofurazane (NBD-Cl) in Mcllvaine buffer	-	510 nm	-	-	73
15	GC-MS	Human Urine	ACN: TEA with OPA (20:80v/v)	Column DB-5MS	290	-	2.92	74

 

 

 

Analytical Method Developed by Fluorescence Spectroscopy:

It is a type of electromagnetic spectroscopy also called fluorimetry and spectroflourometry. The measurement of fluorescence by the instrument called fluorometer, fluorimeter or fluormeter. It works on principle on absorption spectroscopy. (Table-9).

 

Table:-9.

S. No	Method	Sample	Solvent	Wavelength	Ref.
1	Fluorescence Spectroscopy	Tablet	Water	480 nm	(75)

 

CONCLUSION:

This review highlights the analytical method reported on estimation of Quetiapine fumarate on bulk and pharmaceutical formulation. The methods used for determination have high accuracy, high sensitivity, specificity and low cost with minimum interferences. It have consequences that to increase in technologies there are more analytical method are to developed for future evaluation and quality control in formulation.

 

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Received on 05.10.2025      Revised on 22.10.2025 Accepted on 03.11.2025      Published on 06.11.2025 Available online from November 11, 2025 Asian J. Research Chem.2025; 18(6):427-433. DOI: 10.52711/0974-4150.2025.00064 ©A and V Publications All Right Reserved
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