Validated Analytical Approaches for Sitagliptin Monohydrate and Metformin: A Critical Review

Manda Sreekanth, Konda Sri Vaishnavi, Padugula Soumya, Nenavath Kanakaraju, Tadikonda Rama Rao,

doi:10.5281/zenodo.15675876

Review Paper | Open Access
Volume 02 | Issue 06 | Article Id IJSRT/250306048

Validated Analytical Approaches for Sitagliptin Monohydrate and Metformin: A Critical Review
Manda Sreekanth* Konda Sri Vaishnavi Padugula Soumya Nenavath Kanakaraju Tadikonda Rama Rao
Department of Pharmaceutical Chemistry and Analysis, CMR College of Pharmacy, Kandlakoya, Medchal-Malkajgiri-501401, Telangana, India

Abstract

The two main treatments for type 2 diabetes mellitus are sitagliptin and metformin, which are frequently taken together to provide the best possible glycemic control. The objective of this review is to critically assess analytical and bioanalytical methods for measuring metformin and sitagliptin, either separately or together, in biological matrices and pharmaceutical formulations between 2005 and 2025. Titrimetric analysis, spectrophotometry, chromatography (high-performance and ultra-performance liquid chromatography), electroanalytical methods, capillary electrophoresis, and chemometric approaches are among the techniques evaluated. While spectrophotometry delivers routine analysis at a reasonable cost, chromatography offers excellent sensitivity and resilience, making it perfect for complicated matrices. Chemometric techniques improve data interpretation, whereas capillary electrophoresis and electroanalytical techniques guarantee accuracy for particular applications. Each method's validation metrics, including specificity, accuracy, and reproducibility, were examined. Applications include therapeutic monitoring, pharmacokinetic research, and quality control. High equipment expenditures for sophisticated methods and matrix interference in biological samples are among the drawbacks. Method procedures are made clearer by schematic workflows, which also help choose techniques according to matrix complexity, cost, and sensitivity. According to this review, the choice of method is contingent upon the analytical requirements; chromatography is a diverse but resource-intensive technique, while spectrophotometry and other simpler methods are better suited for everyday work. These observations help researchers optimize metformin and sitagliptin measurement techniques, promoting improvements in diabetes care.

Keywords

Sitagliptin, Metformin, Chromatography, Spectrophotometry

Introduction

Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic disorder characterized by persistent hyperglycemia resulting from a combination of insulin resistance and impaired insulin secretion. With the global prevalence of T2DM rising at an alarming rate, it has become a major health concern contributing significantly to morbidity, mortality, and healthcare costs worldwide. The World Health Organization (WHO) has identified diabetes as one of the most critical non-communicable diseases of the 21st century, necessitating effective therapeutic interventions to prevent its associated complications, including nephropathy, neuropathy, retinopathy, and cardiovascular diseases. Sitagliptin and Metformin combination therapy has become a mainstay in the treatment of type 2 diabetes among the several pharmacotherapeutic strategies that are available. By improving the incretin system and selectively inhibiting Dipeptidyl Peptidase-4 (DPP-4), sitagliptin promotes glucose-dependent insulin secretion while blocking glucagon release. Inhibiting hepatic gluconeogenesis and enhancing peripheral insulin sensitivity are the main ways that the biguanide drug metformin reduces blood sugar. These two medications work in concert to improve glycemic control while reducing the risk of weight gain and hypoglycemia. This results in a good safety and effectiveness profile for long-term treatment. According to its chemical designation, sitagliptin is (R)-4-oxo-4-[3-(trifluoromethyl)-5,6-dihydro [1, 2, 4]. triazolo [4,3-a] [pyrazin-7(8H)-yl] The chemical formula for -1-(2,4,5-trifluorophenyl) butan-2-amine is C16H15F6N5O, and its molecular weight is 407.31 g/mol. It is a crystalline powder that ranges from white to off-white and dissolves somewhat in water and somewhat in phosphate buffer. 1,1-dimethylbiguanide hydrochloride, the chemical name for metformin, is a white, crystalline substance with a molecular weight of 165.63 g/mol, a molecular formula of C4H11N5•HCl, and a high-water solubility. Both medications are recognized by several pharmacopoeias, including as the IP, BP, and USP. Numerous analytical techniques have been developed to precisely quantify sitagliptin and metformin in bulk materials, pharmaceutical formulations, and biological matrices due to their growing use as monotherapy and in fixed-dose combos. UV-visible spectrophotometry, capillary electrophoresis, high-performance liquid chromatography (HPLC), ultra-performance liquid chromatography (UPLC), electroanalytical techniques, and hyphenated techniques like LC-MS/MS are among the methods used for their analysis. The goal of this review is to present a thorough and critical analysis of the analytical methods used for sitagliptin and metformin estimates in the literature from 2006 to 2024. These techniques fall into the following analytical domains: (1) spectrophotometric techniques, (2) chromatographic techniques, (3) electroanalytical approaches, (4) capillary electrophoretic techniques, and (5) hyphenated and chemometric-assisted strategies. It covers the development, benefits, drawbacks, and applicability of these techniques. This article intends to assist researchers, pharmaceutical analysts, and regulatory professionals in choosing suitable techniques for the qualitative and quantitative evaluation of sitagliptin and metformin in various matrices by providing a thorough and structured overview of the current analytical landscape.

Fig.1.Sitagliptin

Fig. 2. Metformin

Figure 3. Proportion of analytical methods available for the estimation of metformin and sitagliptin

Figure 4. Relative proportion of matrices analyzed for metformin and Sitagliptin

Mechanism of Action Sitagliptin

Mechanism of Action Metformin

Validated Analytical Techniques

Method

Analyte

Matrix

Key Parameters

Validation Parameters

References

Titrimetric Analysis

Metformin

Bulk, Tablets

Redox titration with potassium permanganate in acidic medium

LOD: 0.5 µg/mL, LOQ: 1.5 µg/mL, Precision: <2% RSD, Accuracy: 98.5–101.5%, Robustness: Stable across pH 2–4

[1]

UV/Visible Spectrophotometry

Sitagliptin

Tablets

Charge-transfer complex with chloranilic acid, λ = 520 nm, linearity: 5–50 µg/mL

LOD: 0.8 µg/mL, LOQ: 2.4 µg/mL, Precision: <1.5% RSD, Accuracy: 99.0–100.8%, Robustness: Stable with ±5% reagent variation

[2]

UV/Visible Spectrophotometry

Metformin

Tablets

Derivatization with ninhydrin, λ = 400 nm, linearity: 10–100 µg/mL

LOD: 1.2 µg/mL, LOQ: 3.6 µg/mL, Precision: <2% RSD, Accuracy: 98.2–101.2%, Robustness: Stable at 25–30°C

[3]

UV/Visible Spectrophotometry

Sitagliptin + Metformin

Tablets

Simultaneous equation method, λ = 267 nm (sitagliptin), 232 nm (metformin), linearity: 5–50 µg/mL (both)

LOD: 0.5 µg/mL (sitagliptin), 1.0 µg/mL (metformin), LOQ: 1.5 µg/mL (sitagliptin), 3.0 µg/mL (metformin), Precision: <1.8% RSD, Accuracy: 98.5–101.5%, Robustness: Stable with ±10% solvent variation

[4]

Spectrofluorimetry

Sitagliptin

Tablets

Sodium dodecyl sulfate micellar medium, excitation/emission: 270/430 nm, linearity: 0.1–2.0 µg/mL

LOD: 0.03 µg/mL, LOQ: 0.1 µg/mL, Precision: <1.2% RSD, Accuracy: 99.2–100.5%, Robustness: Stable with ±0.5 pH units

[5]

Spectrofluorimetry

Sitagliptin + Metformin

Tablets

Excitation/emission: 265/425 nm (sitagliptin), derivatization for metformin, linearity: 0.2–5 µg/mL (sitagliptin), 10–100 µg/mL (metformin)

LOD: 0.05 µg/mL (sitagliptin), 2.0 µg/mL (metformin), LOQ: 0.15 µg/mL (sitagliptin), 6.0 µg/mL (metformin), Precision: <2.5% RSD, Accuracy: 98.0–101.8%, Robustness: Stable with ±5% surfactant concentration

[6]

High-Performance Liquid Chromatography (HPLC)

Sitagliptin

Tablets

C18 column, mobile phase: acetonitrile: phosphate buffer (60:40), UV detection at 267 nm, linearity: 10–100 µg/mL

LOD: 0.3 µg/mL, LOQ: 1.0 µg/mL, Precision: <1.5% RSD, Accuracy: 99.0–100.9%, Robustness: Stable with ±5% flow rate variation

[7]

High-Performance Liquid Chromatography (HPLC)

Metformin

Tablets

C18 column, mobile phase: methanol: water (70:30), UV detection at 232 nm, linearity: 20–200 µg/mL

LOD: 0.6 µg/mL, LOQ: 2.0 µg/mL, Precision: <2% RSD, Accuracy: 98.5–101.0%, Robustness: Stable with ±10% organic phase variation

[8]

High-Performance Liquid Chromatography (HPLC)

Sitagliptin + Metformin

Tablets

C18 column, mobile phase: acetonitrile: phosphate buffer (50:50), UV detection at 260 nm, linearity: 5–50 µg/mL (both)

LOD: 0.2 µg/mL (sitagliptin), 0.4 µg/mL (metformin), LOQ: 0.6 µg/mL (sitagliptin), 1.2 µg/mL (metformin), Precision: <1.5% RSD, Accuracy: 98.8–101.2%, Robustness: Stable with ±0.2 pH units

[9]

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)

Sitagliptin + Metformin

Human Plasma

C18 column, mobile phase: methanol: ammonium acetate, ESI-MS/MS, linearity: 0.05–50 ng/mL (sitagliptin), 1–1000 ng/mL (metformin)

LOD: 0.02 ng/mL (sitagliptin), 0.3 ng/mL (metformin), LOQ: 0.05 ng/mL (sitagliptin), 1.0 ng/mL (metformin), Precision: <3% RSD, Accuracy: 97.5–102.0%, Robustness: Stable with ±10% extraction solvent

[10]

Ultra-Performance Liquid Chromatography (UPLC)

Sitagliptin + Metformin

Tablets

C18 column, mobile phase: methanol: ammonium acetate (70:30), UV detection at 265 nm, run time: 3 min, linearity: 2–20 µg/mL (both)

LOD: 0.1 µg/mL (both), LOQ: 0.3 µg/mL (both), Precision: <1.2% RSD, Accuracy: 99.0–101.0%, Robustness: Stable with ±5% pressure variation

[11]

High-Performance Thin-Layer Chromatography (HPTLC)

Sitagliptin

Tablets

Silica gel plates, mobile phase: methanol: ammonia (8:2), densitometry at 267 nm, linearity: 100–1000 ng/spot

LOD: 30 ng/spot, LOQ: 90 ng/spot, Precision: <2% RSD, Accuracy: 98.5–101.5%, Robustness: Stable with ±5% mobile phase composition

[12]

High-Performance Thin-Layer Chromatography (HPTLC)

Sitagliptin + Metformin

Tablets

Silica gel plates, mobile phase: methanol: ammonia: ethyl acetate (7:2:1), densitometry at 260 nm, linearity: 100–1000 ng/spot (both)

LOD: 25 ng/spot (sitagliptin), 40 ng/spot (metformin), LOQ: 75 ng/spot (sitagliptin), 120 ng/spot (metformin), Precision: <1.8% RSD, Accuracy: 98.0–101.8%, Robustness: Stable with ±10% chamber saturation time

[13]

Differential Pulse Voltammetry

Sitagliptin

Tablets

Carbon paste electrode, pH 7.0 phosphate buffer, linearity: 0.05–10 µg/mL

LOD: 0.01 µg/mL, LOQ: 0.03 µg/mL, Precision: <2.5% RSD, Accuracy: 98.2–101.5%, Robustness: Stable with ±0.5 pH units

[14]

Square-Wave Voltammetry

Metformin

Tablets

Glassy carbon electrode, pH 6.5 buffer, linearity: 0.5–50 µg/mL

LOD: 0.1 µg/mL, LOQ: 0.3 µg/mL, Precision: <2% RSD, Accuracy: 98.5–101.0%, Robustness: Stable with ±5% scan rate variation

[15]

Capillary Electrophoresis (CE)

Sitagliptin

Tablets

Phosphate buffer with β-cyclodextrin, UV detection at 267 nm, run time: 8 min, linearity: 1–50 µg/mL

LOD: 0.2 µg/mL, LOQ: 0.6 µg/mL, Precision: <1.5% RSD, Accuracy: 99.0–100.8%, Robustness: Stable with ±5% buffer concentration[

[16]

Capillary Electrophoresis (CE)

Sitagliptin + Metformin

Tablets

Borate buffer, pH 9.0, UV detection at 260 nm, linearity: 2–100 µg/mL (both)

LOD: 0.3 µg/mL (sitagliptin), 0.5 µg/mL (metformin), LOQ: 1.0 µg/mL (sitagliptin), 1.5 µg/mL (metformin), Precision: <2% RSD, Accuracy: 98.5–101.5%, Robustness: Stable with ±0.2 pH units

[17]

Chemometric-Assisted Spectrophotometry

Sitagliptin + Metformin

Tablets

Partial least squares (PLS) model, λ = 230–270 nm, linearity: 5–50 µg/mL (both)

LOD: 0.4 µg/mL (sitagliptin), 0.8 µg/mL (metformin), LOQ: 1.2 µg/mL (sitagliptin), 2.4 µg/mL (metformin), Precision: <1.5% RSD, Accuracy: 98.0–102.0%, Robustness: Stable with ±5% wavelength variation

[18]

Chemometric-Assisted HPLC

Sitagliptin + Metformin

Biological Fluids

Principal component regression (PCR), C18 column, linearity: 0.1–10 µg/mL (both)

LOD: 0.03 µg/mL (sitagliptin), 0.05 µg/mL (metformin), LOQ: 0.1 µg/mL (sitagliptin), 0.15 µg/mL (metformin), Precision: <2.5% RSD, Accuracy: 97.8–102.2%, Robustness: Stable with ±5% flow rate variation

[19]

Method Type	Analytes	Matrix	Key Method Parameters	Validation Results	Greenness	Reference
RP-HPLC (Monolithic C18)	Sitagliptin & Metformin	Bulk, Tablets	Mobile Phase: Methanol: Acetonitrile, pH 3.5; Detection at 210 nm; Flow Rate: 0.484 mL/min; Retention: 3.3 min (Metformin), 4.4 min (Sitagliptin)	Accuracy: Within 98–102%; Precision: %RSD < 2%; Robustness confirmed by AQbD	Not specified	[20]
RP-HPLC (Methanol-Buffer)	Metformin, Linagliptin, Empagliflozin	Human Plasma	Mobile Phase: Methanol: Phosphate buffer (65.6:34.4 v/v); Detection at 225 nm; Flow Rate: 1 mL/min	LOD: 0.043 µg/mL (Metformin); LOQ: 0.130 µg/mL (Metformin); Accuracy: 98–102%; Precision: %RSD <2%	Eco-Scale Score: 73	[21]
UPLC (Ethanol-based)	Metformin & Empagliflozin	Tablets	Mobile Phase: Ethanol: Ammonium acetate; Detection at 265 nm; Run Time: 3 min	LOD: 0.1 µg/mL; LOQ: 0.3 µg/mL; Accuracy: 99–101%; Precision: <1.2% RSD	AGREE Score: 0.89	[22]
Micellar LC (SDS + Brij-35)	Sitagliptin & Metformin	Tablets	Organic solvent-free mobile phase; Detection at 267 nm; Micellar solution	LOD: 0.1 µg/mL; LOQ: 0.3 µg/mL; Accuracy: 98–102%; Precision: %RSD <2%	AGREE Score: 0.85	[23]
HPTLC (Ethanol: Water)	Metformin, Pioglitazone, Teneligliptin	Tablets	Mobile Phase: Ethanol: Water; Densitometry at 260 nm	LOD: 25 ng/spot; LOQ: 75 ng/spot; Accuracy: 98–101.8%; Precision: %RSD <1.8%	AGREE Score: 0.92	[24]
RP-HPLC (RSM optimized)	Metformin, Vildagliptin, Dapagliflozin, Sitagliptin	Bulk, Tablets	Mobile Phase: Methanol: Buffer; Detection at 260 nm; RSM optimization	LOD: 0.2–0.4 µg/mL; LOQ: 0.6–1.2 µg/mL; Accuracy: 98.8–101.2%; Precision: <1.5% RSD	Greenness Score: 0.86	[25]
RP-HPLC (Full factorial AQbD)	Omarigliptin, Metformin, Ezetimibe	Plasma, Tablets	Mobile Phase: Methanol: Ammonium acetate; Detection at 260 nm	LOD: 0.03 µg/mL (Metformin); LOQ: 0.1 µg/mL (Metformin); Accuracy: 97.5–102%; Precision: <3% RSD	Not specified	[26]

1.Volumetric Methods

For metformin, a redox titration technique employing potassium permanganate in an acidic medium has been documented, validated in accordance with ICH recommendations. However, there are no known titrimetric techniques for sitagliptin, most likely because of its intricate structure, which makes direct titration more difficult. Finding the volume of a solution with a given concentration needed to react with a measured volume of the material to be examined is the goal of titrmetric analysis. Although there aren't many particular titrimetric techniques for metformin and sitagliptin, spectrophotometric techniques are frequently employed. An ion-pair technique employing methyl orange has been devised for sitagliptin, while oxidation with potassium permanganate in an alkaline media is used for metformin. Both approaches ensure accuracy in pharmaceutical analysis by adhering to ICH validation requirements.

2. Optical Methods

UV/Visible Spectrophotometry

Pharmaceutical analysis frequently uses UV/visible spectrophotometry because it is easy to use, reasonably priced, and appropriate for routine quality control—especially in situations where sophisticated instruments are not accessible. Measuring sitagliptin involves charge-transfer compounds with chloranilic acid (520 nm), whereas metformin is derivatized with ninhydrin (400 nm). Second-derivative spectroscopy at zero-crossing sites, area under curve (AUC) analysis, and the simultaneous equation method (absorption maxima at 267/237 nm or 266/232 nm) are examples of simultaneous estimation techniques. According to ICH recommendations, these methods have been tested and offer reliability, although their sensitivity for trace biological analysis is restricted. The main target of spectrofluorimetric techniques, which are renowned for their simplicity and excellent sensitivity, is sitagliptin, whose fluorescence is increased by micellar medium such as SDS. Excitation/emission at 270/430 nm, micelle-enhanced detection at 300 nm, and derivatization with o-phthalaldehyde to create a fluorescent isoindole derivative are among the detecting techniques.
In multi-drug formulations, simultaneous estimation with sitagliptin has been produced despite metformin's lack of natural fluorescence. These proven techniques work well for analyzing biological and pharmacological fluids, but they need to be carefully adjusted to reduce interference.

3. Chromatographic Methods

High-Performance Liquid Chromatography (HPLC)

HPLC is a widely used, robust, and versatile technique for the simultaneous quantification of sitagliptin and metformin in pharmaceutical formulations. Reverse-phase HPLC using C18 columns and UV detection at 260–270 nm, with mobile phases like acetonitrile:phosphate buffer mixtures, is common. Methods often employ gradient elution, providing high sensitivity, accuracy, and reliability for routine analysis. For biological samples, LC-MS/MS offers superior sensitivity, detecting sitagliptin in plasma with linearity from 0.05–50 ng/mL. Forced degradation studies ensure method specificity.

Ultra-Performance Liquid Chromatography (UPLC)

Higher pressures and smaller particle sizes allow Ultra-Performance Liquid Chromatography (UPLC) to analyze data more quickly and with higher resolution than HPLC. With run times as short as three minutes, UPLC techniques for sitagliptin and metformin together employ C18 columns with methanol: ammonium acetate mobile phases. High-throughput analysis is best served by these techniques, but they do require certain tools.
Ultra-Performance Liquid Chromatography (UPLC): UPLC is superior to conventional HPLC in terms of resolution and analysis speed. For the study of metformin and sitagliptin, optimized UPLC techniques have been developed, employing gradient mobile phases and columns such as Hypersil C18. For the quantification of the medications in pharmaceutical formulations, these techniques offer quick, effective, and precise findings, which makes UPLC an important tool for quality control.

Thin-Layer Chromatography (TLC/HPTLC)

TLC/HPTLC, orthin-layerchromatography For simultaneous quantification, high-performance thin-layer chromatography (HPTLC) techniques employ silica gel plates with mobile phases such as methanol: ammonia. The ability to analyze numerous samples at once using HPTLC reduces analysis time and solvent usage. Both medications have been found to have linearity ranges of 100–1000 ng/spot.

High-Performance Thin-Layer Chromatography (HPTLC):

Pharmaceutical analysis can be done with High-Performance Thin-Layer Chromatography (HPTLC), a simple and affordable chromatographic method. For the simultaneous measurement of sitagliptin and metformin in bulk and tablet dose forms, an HPTLC approach has been devised and validated. Using a particular solvent system and detection wavelength, this technique provides a dependable and effective substitute for standard pharmaceutical product quality control

4.ElectroanalyticalMethods

High sensitivity, accuracy, and cost-effectiveness make electroanalytical methods—like voltammetry—suitable for regular clinical and pharmaceutical analysis. Square-wave voltammetry has been used to quantify metformin through its electrochemical reduction, whereas differential pulse voltammetry has been created for sitagliptin utilizing carbon paste electrodes, with a detection limit of 0.01 µg/mL. Although these techniques offer rapid and accurate measurements, matrix effects in biological samples must be addressed through optimization.

5. Capillary Electrophoresis (CE)

High resolution is provided by CE techniques for the separation of metformin and sitagliptin enantiomers in intricate matrices. To separate sitagliptin enantiomers, a phosphate buffer approach with cyclodextrin as a chiral selector was used, and it took eight minutes. Due to the high polarity of metformin, CE is less prevalent; nonetheless, hybrid techniques that combine electrophoresis and electrochromatography show potential. Although CE is extremely sensitive, it needs operators with expertise.

6. Bioanalytical Methods

Pharmacokinetic, bioavailability, and bioequivalence investigations of metformin and sitagliptin require the use of bioanalytical techniques. The gold standard, LC-MS/MS, provides high sensitivity with quantification limits as low as 0.1 ng/mL, facilitated by solid-phase extraction and liquid-liquid sample preparation methods. With linearity ranges of 0.5–500 ng/mL, sitagliptin, metformin, and their metabolites have all been quantified simultaneously. In order to facilitate therapeutic monitoring in clinical settings, fluorescence-based techniques have also been investigated, especially for sitagliptin.

7. Chemometric Methods

Particularly in complicated matrices with overlapping spectra, chemometric methods like principal component regression (PCR) and partial least squares (PLS) increase the precision and accuracy of spectrophotometric and chromatographic analysis of metformin and sitagliptin. In tablets, a PLS-based approach produced medication recoveries of 98–102%. Chemometrics is especially useful when interference makes established approaches difficult to use.

Schematic representation of all analytical methods

Name of Analytical Method	Schematic Workflow
Titrimetric Analysis	[Sample (Metformin)] → Dissolve in acidic medium → Titrate with KMnO4 → Endpoint detection (color change) → Calculate concentration
Spectrophotometric Methods	[Sample] → Dissolve in solvent → Add reagent (e.g., chloranilic acid) → Measure absorbance at λmax → Calculate concentration using calibration curve
Spectrophotometric Methods	[Sample] → Add micellar medium (e.g., SDS) → Measure fluorescence intensity → Quantify using calibration curve
Chromatographic Methods	[Sample] → Extract → Inject into HPLC → Separate on C18 column → Detect at 260 nm → Quantify via peak area
	[Plasma Sample] → Liquid-liquid extraction → Inject into LC-MS/MS → Separate on C18 column → Detect via MRM → Quantify
	[Sample] → Apply to silica gel plate → Develop with mobile phase → Scan densitometrically at 260 nm → Quantify
Electroanalytical Methods	[Sample] → Dissolve in buffer → Apply to electrode → Measure current response → Quantify via peak current
Capillary Electrophoresis (CE)	[Sample] → Inject into capillary → Apply voltage → Separate in buffer → Detect at 260 nm → Quantify
Chemometric Methods	[Sample] → Acquire spectra → Apply PLS/PCR model → Predict concentrations

DISCUSSION

Biguanide, and sitagliptin, a well-known DPP-4 inhibitor, have drawn a lot of interest in a variety of pharmacological formulations. The most used procedures for measuring sitagliptin and metformin are UV/visible spectrophotometry and HPLC. Studies have shown that capillary electrophoretic and electroanalytical techniques are available for accurately identifying these medications in pharmaceutical formulations. Owing to the difficulties with solubility, solvents such as methanol or acetonitrile are frequently employed in sample preparation to increase sensitivity the best way to analyze sitagliptin and metformin in biological fluids and pharmaceutical formulations is to use HPLC with UV detection. The measurement of these medications in biological matrices is also increasingly being done using LC-MS/MS techniques, which provide better sensitivity and selectivity than HPLC-UV. Moreover, sitagliptin and metformin have been simultaneously determined using recent developments in chemometrics, both separately and in combination. Even with advancements, the ongoing creation of innovative methods is still necessary to get greater sensitivity and precision in their quantification.

CONCLUSION

sitagliptin and metformin in pharmaceutical dose forms and biological fluids, both alone and in combination with other medications, using spectrofluorimetric and chromatographic methods. It is clear that sitagliptin and metformin, either separately or in combination, are mostly analyzed using liquid chromatographic techniques. Although there are established, validated techniques for measuring and ensuring the quality of these medications, the majority of them do not follow "green chemistry" guidelines. Thus, future research should concentrate on creating environmentally friendly techniques for estimating the levels of metformin and sitagliptin in biological matrices and pharmaceutical formulations. This strategy might lessen the need for hazardous organic solvents and the environmental risks connected to their disposal.

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