Sigma Institute of Pharmacy, Sigma University, Bakrol,, Vadodara, Gujarat, India 390019
Polycystic ovary syndrome (PCOS) is a common endocrine–metabolic disorder marked by insulin resistance, hyperandrogenism, and ovulatory dysfunction, resulting in menstrual irregularities, infertility, and increased metabolic risk. Metformin improves insulin sensitivity and reduces hepatic glucose production, thereby indirectly decreasing androgen levels and improving metabolic and reproductive function. Spironolactone, owing to its antiandrogenic activity, is effective in controlling symptoms such as hirsutism and acne. Their combined use provides a rational therapeutic strategy by addressing both metabolic and hormonal abnormalities of PCOS. In addition to clinical management, accurate pharmaceutical analysis is essential to ensure drug quality, safety, and efficacy. Analytical techniques including RP-HPLC, UV spectrophotometry, and HPTLC are widely employed for method development, validation, and stability studies of these drugs. This review summarizes the pathophysiology, treatment approach, and analytical evaluation of metformin and spironolactone in PCOS.
PCOS (Polycystic ovary syndrome): [1,2]
Polycystic ovary syndrome is a common metabolic and reproductive disorder characterized variably by high levels of androgens, insulin resistance, and ovulatory dysfunction, with not all patients affected by these three parameters. These alterations show up as oligomenorrhea or amenorrhea, structural characteristics of polycystic ovaries on ultrasonography, and hyperandrogenism (hirsutism, acne, or scalp hair loss, or a combination of these). Polycystic ovarian syndrome, which has long been recognized as a reproductive issue, is now known to be a metabolic disorder linked to long-term health hazards, such as cardiovascular disease and type 2 diabetes.
Worldwide, a large number of women of reproductive age suffer with the diverse endocrine condition known as polycystic ovarian syndrome (PCOS). Excess androgen levels, insulin resistance, oversized and dysfunctional ovaries, and other conditions are frequently linked to this syndrome. According to estimates, over 10% of women get PCOS before to menopause and deal with its aftereffects.
Pathophysiology [3,4]:
Figure-1: Pathophysiology of PCOS.
Polycystic ovary syndrome (PCOS) develops mainly because of a disturbance in insulin action and reproductive hormone balance. In many women with PCOS, body tissues such as the liver and muscles do not respond effectively to insulin, so the pancreas produces higher levels of insulin to keep blood sugar normal. This excess insulin directly stimulates the ovaries to produce more androgens (male-type hormones). Elevated androgen levels interfere with the normal development and maturation of ovarian follicles, which prevents regular ovulation. At the same time, hormonal signa-ling from the brain becomes altered, resulting in an imbalance between luteinizing hormone (LH) and follicle-stimulating hormone (FSH), further disturbing ovarian function. Because of these changes, ovulation becomes irregular or may stop completely, menstrual cycles become abnormal, and immature follicles accumulate in the ovaries. These hormonal disturbances also worsen insulin resistance, creating a continuous cycle in which metabolic and hormonal abnormalities reinforce each other. Thus, PCOS is a self-maintaining disorder where insulin resistance and excess androgen production together lead to reproductive and metabolic complications.
Causes of PCOS:
Treatment of PCOS:
Introduction to Drug: [5,6]
METFORMIN: [5]
The FDA approved METFORMIN in 1995.
Metformin acts mainly as an insulin sensitizer by reducing hepatic glucose production, enhancing insulin sensitivity, and lowering circulating insulin levels. This reduction in hyperinsulinemia indirectly decreases ovarian androgen production, improving menstrual regularity and metabolic function.
Metformin mainly works by lowering blood sugar without increasing insulin release. It reduces glucose production in the liver, so less sugar enters the blood. It improves insulin sensitivity, helping body cells use glucose more effectively. It slows glucose absorption from the intestine, which prevents sudden sugar spikes after meals.
SPIRONOLACTONE: [6]
The FDA approve SPIRONOLACTONE in 1960.
Spironolactone is a potassium-sparing diuretic and aldosterone antagonist used to treat conditions such as hypertension, heart failure, edema, and primary hyperaldosteronism. It blocks aldosterone receptors in the distal renal tubules of the kidney, promoting sodium and water excretion while sparing potassium. Besides its diuretic effect, spironolactone exhibits antiandrogenic properties, making it effective in treating androgen-related disorders like hirsutism, acne, and polycystic ovary syndrome (PCOS). Its diverse actions contribute to cardiovascular and hormonal disease management. Research supports its role in improving fluid balance and reducing blood pressure alongside other therapies.
Rationale of the work:
Metformin is a first-line antidiabetic agent, while Spironolactone is a potassium-sparing diuretic used for conditions such as hypertension and PCOS. Combination therapy involving these drugs may offer improved management of metabolic disorders such as insulin resistance with cardiovascular complications.
The combination of metformin plus spironolactone is rational in PCOS because it targets dual pathophysiology: insulin resistance via metformin and androgen excess via spironolactone. The registered trial NCT03981861 specifically tests metformin (500 mg BID) + spironolactone (50 mg QD) over 6 months in adolescents with PCOS to evaluate metabolic and neuroendocrine outcomes. Published clinical data and meta-analysis support that the combo more effectively lowers BMI and total testosterone, and improves glucose / insulin indices more than metformin alone, without significant increase in adverse events. However, risks include hyperkalemia, worsening renal load, and potential interaction altering glycemic control; thus, careful patient selection, baseline labs, and periodic monitoring are crucial.
LITERATURE REVIEW:
Literature review of Metformin:
Table 1: Literature review of Metformin
|
Sr. No. |
Title |
Method |
Description |
Ref No. |
|
|
1 |
Indian Pharmacopoeia Volume-II |
IP |
Mobile phase: Solution Containing 0.087 percent w/v of Sodium chloride, adjusted to pH 3.5 using 1%v/v solution of Orthophosphoric acid Stationary phase: A stainless-steel column (30 cm × 4 mm, 10 µm) packed with octadecylsilane bonded to silica Wavelength: 218 nm Flow rate: 1ml/min |
7 |
|
|
2 |
British Pharmacopoeia Volume-II |
BP |
Mobile phase: Acetonitrile: 0.05 M KH?PO? buffer (pH 3.5): acetonitrile (84:16 % v/v) Stationary phase: Stainless steel column (12.5 cm × 4.5 cm, 5 µm) packed with strong cation-exchange silica gel (or Luna SCX) Wavelength: 218 nm Flow rate: 1 ml/min |
8 |
|
|
3 |
United Stat Pharmacopoeia- National Formulary Volume-III |
USP |
Mobile phase: Prepare solution in water, containing 17 g of monobasic ammonium phosphate per L, adjust with phosphoric acid to pH of 3.0 and mix Stationary phase: 3.9 mm × 30 cm, 10 µm packing, L1 Wavelength: 218 nm Flow rate: 1 ml/min |
9 |
|
|
4 |
Development and Validation of UV?Spectroscopic Method Development and Validation for the Estimation of Metformin HCl in Pure and Its Marketed Tablets |
UV |
Solvent: Acetonitrile: Methanol: Water = 1:1:1 λ max: 298 nm Linearity: 1?50?µg/mL
|
10 |
|
|
5 |
Quantitative UV?Spectrophotometric Method for the Analysis of Teneligliptin?HBr and Metformin?HCl in Pharmaceutical Dosage Form |
UV |
Solvent: 0.1?N Sulfuric acid λ max: 220?nm for (Metformin?HCl) and 240 nm for (Teneligliptin?HBr) Linearity: 100 µg /ml |
11 |
|
|
6 |
Development and Validation of UV Spectrophotometric Method for Simultaneous Estimation of Sitagliptin and Metformin in Bulk & Combined Formulation |
UV |
Solvent: Distilled water λ max: 237?nm for (Metformin) and 267 nm for (Sitagliptin) Linearity: 4?14?µg/mL for (Metformin) and10-300 µg/ml for (Sitagliptin) |
12 |
|
|
7 |
Development and Validation of Green UV Derivative Spectrophotometric Methods for Simultaneous Determination of Metformin and Remogliflozin |
UV |
Solvent: Water λ max: 252.2?nm for (Metformin) and 233.0 nm for (Remogliflozin) Linearity: 2.5?35?µg/mL for (Metformin) and1-20 µg/ml for (Remogliflozin) |
13 |
|
|
8 |
Spectrophotometric Method Development and Validation for Simultaneous Estimation of Anagliptin and Metformin HCl by Q?Absorption Ratio Method in Synthetic Mixture |
UV |
Solvent: Distilled Water λ max: 233?nm for (Metformin) and 238 nm for (Anagliptin) Linearity: 5?30?µg/mL for (Metformin) and 2-12 µg/mL for (Anagliptin) |
14 |
|
|
9 |
Method Development, Validation & Stress Studies of Dapagliflozin and Metformin Hydrochloride Using UV?Vis Spectroscopy |
UV |
Solvent: Water as diluent λ max: 232 nm for (Metformin) and 222 nm for (Dapagliflozin) Linearity: 1–20μg/ml for (Metformin) and 2 – 32μg/ml for (Dapagliflozin) |
15 |
|
|
10 |
Simultaneous Assays of Metformin HCl and Glibenclamide Mixture Using Spectrophotometry Methods |
UV |
Solvent: Water λ max: 230?240?nm for (Metformin) and 225-235 nm for (Glibenclamide) Linearity: linearity = 0.9881 for (Metformin) and linearity = 0.9993 for (Glibenclamide) |
16 |
|
|
11 |
Development and Validation of UV?Spectrophotometric Method for Estimation of Metformin?HCl and Pioglitazone in Tablet Dosage Form |
UV |
Solvent: Methanol λ max: 232.4 nm and 241.8 nm for (Metformin) and 264.8 nm and 272.8 nm for (Pioglitazone) Linearity: 5?40?µg/mL |
17 |
|
|
12 |
Estimation of Metformin Hydrochloride by UV?Spectroscopic Area Under Curve Method |
UV |
Solvent: Distilled water λ max: 221-241 nm Linearity: 5?25?µg/mL
|
18 |
|
|
13 |
Development and Validation of UV?Spectrophotometric Method for Simultaneous Estimation of Metformin HCl and Repaglinide in Pharmaceutical Formulation |
UV |
Solvent: Methanol λ max: 238 nm for (Metformin HCL) and 294 nm for (Repaglinide)
Linearity: 2?100?µg/mL for (Metformin) and 1-35 µg/ml for (Repaglinide) |
19 |
|
|
14 |
Development and Validation of UV Spectrophotometric Method for Estimation of Metformin in Bulk & Tablet Dosage Form |
UV |
Solvent: Water λ max: 234?nm Linearity: 10-50?µg/mL |
20 |
|
|
15 |
Estimation of Metformin Hydrochloride by UV Spectrophotometric Method in Pharmaceutical Formulation |
UV |
Solvent: Distilled water λ max: 232?nm Linearity: 2-10 µg/mL |
21 |
|
|
16 |
A novel RP-HPLC approach for simultaneous determination of Dapagliflozin, Linagliptin, and Metformin in pharmaceutical formulations |
HPLC |
Mobile phase: Acetonitrile / Phosphate buffer (pH 6.8) = (40:60%v/v) Stationary phase: Phenomenex Luna C?? (250 × 4.6 mm, 5 µm) Wavelength: 230 nm Flow rate: 0.80 ml/min |
22 |
|
|
17 |
Development and Validation of HPLC Method for the Estimation of Metformin HCl and Anagliptin in its Synthetic Mixture |
HPLC |
Mobile phase: Buffer: Acetonitrile = (80:20%v/v) (pH 3.0) Stationary phase: C?? (250 × 4.6 mm, 5 µm) Wavelength: 232 nm Flow rate: 1 ml/min |
23 |
|
|
18 |
Analytical method of development and validation for determination of Canagliflozin and Metformin in API and synthetic mixture by RP-HPLC |
HPLC |
Mobile phase: Acetonitrile: Phosphate buffer (pH 3.5) = (70:30%v/v) Stationary phase: C?? column (250×4.6 mm, 5 µm) Wavelength: 254 nm Flow rate: 1 ml/min |
24 |
|
|
19 |
Development And Validation Of RP-HPLC Method For Anagliptin and Metformin Hydrochloride and Its Related Impurities In Tablet Dosage Form
|
HPLC |
Mobile phase: Acetonitrile: 0.05 M Potassium dihydrogen phosphate buffer (pH 3.0) = (50 :50 %v/v) Stationary phase: Kromasil C?? column (250×4.6 mm, 5 µm) Wavelength: 220 nm Flow rate: 1 ml/min |
25 |
|
|
20 |
Stability Indicating Assay Method of Metformin, Linagliptin and Empagliflozin in Pharmaceutical Dosage Form by HPLC Method |
HPLC |
Mobile phase: Water: Acetonitrile (65:35% v/v) Stationary phase: C18 column (4.6?mm × 25?cm; 5?µm) Wavelength: 269 nm Flow rate: 1 ml/min |
26 |
|
|
21 |
Development and validation of RP?HPLC method for simultaneous estimation of Imeglimin and Metformin |
HPLC |
Mobile phase: Water: Acetonitrile = (50:50%v/v) Stationary phase: Hypersil?C18 (4.6 × 250 mm, 5 µm) Wavelength: 244 nm Flow rate: 1 ml/min |
27 |
|
|
22 |
Analytical quality?by?design approach for development and validation of HPLC method for the simultaneous estimation of Omarigliptin, Metformin, and Ezetimibe |
HPLC |
Mobile phase: Methanol: 6.6?mM KH?PO? buffer (pH?7) = (67?:33% v/v) Stationary phase: Hypersil?BDS?C18 column Wavelength: 235 nm Flow rate: 0.814 ml/min |
28 |
|
|
23 |
A novel RP-HPLC method development and validation for the quantification of a potential anti-diabetic drug Metformin Hydrochloride in tablet dosage form. |
HPLC |
Mobile phase: Buffer (Tetra-Butyl Ammonium Hydroxide 0.002 %) : Acetonitrile (70:30 % v/v) Stationary phase: Shimadzu Shim-pack GIST C?? (5 µm × 4.6 × 250 mm) Wavelength: 232 nm Flow rate: 0.50 ml/min |
29 |
|
|
24 |
Impurity profiling method development and validation of Metformin Hydrochloride and Teneligliptin Hydrobromide hydrate in their combination tablet dosage form by using RP-HPLC with UV/PDA detector |
HPLC |
Mobile phase: Mobile Phase A: (pH 3.0) Buffer Mobile Phase B: Methanol Stationary phase: BDS Hypersil C?? (250 × 4.6 mm, 5 µm) Wavelength: 210 nm Flow rate: 1.0ml/min |
30 |
|
|
25 |
Development and validation of stability?indicating RP?HPLC method for the simultaneous determination of Ertugliflozin pidolate and Metformin HCl in bulk and tablets |
HPLC |
Mobile phase: 0.1% ortho?phosphoric acid buffer (pH?2.7) : Acetonitrile = (65:35% v/v) Stationary phase: Kromasil?C18 (150 × 4.6 mm, 5 µm) Wavelength: 224 nm Flow rate: 1 ml/min |
31 |
|
|
26 |
Development and Validation of RP-HPLC Method for Simultaneous Estimation of Metformin Hydrochloride and Glipizide in Bulk and Pharmaceutical Dosage Form |
HPLC |
Mobile phase: Methanol: Water = (60:40%v/v) Stationary phase: Cosmosil C?? (250×4.6 mm, 5 µm) Wavelength: 220 nm Flow rate: 1 ml/min |
32 |
|
|
27 |
Development and validation of a new analytical HPLC method for simultaneous determination of the antidiabetic drugs, metformin and gliclazide. |
HPLC |
Mobile phase: ammonium formate buffer (pH 3.5): acetonitrile (45:55% v/v) Stationary phase: Alltima CN (250 × 4.6 mm, 5 µm) Wavelength: 227 nm Flow rate: 1.0 ml/min |
33 |
|
|
28 |
Development of new validated HPTLC Method for simultaneous estimation of Canagliflozin and Metformin in Tablet Formulation |
HPTLC |
Mobile Phase: Toluene: Methanol: Triethylamine: Glacial Acetic Acid = (7: 2.6: 0.2: 0.2 %v/v/v/v) Stationary phase: Pre-coated silica gel 60 F????? aluminium sheet λ max: 254 nm Concentration range: 250–2500 ng / band for Metformin, 75-750ng/band of Canagliflozin |
34 |
|
|
29 |
A Sensitive HPTLC Method for the Estimation of Glibenclamide, Rosiglitazone Maleate and Metformin Hydrochloride from a Multicomponent Dosage Form |
HPTLC |
Mobile Phase: Methanol: Tetrahydrofuran: Water: Glacial Acetic Acid = (16: 3.6: 4: 0.4% v/v) Stationary phase: Pre-coated RP-18 F254s aluminum sheets λ max: 214 nm Concentration range: 120–600 ng / band for Metformin 200–1000 ng / band for Glibenclamide 200–1000 ng / band for Rosiglitazone Maleate |
35 |
|
|
30 |
A Novel Validated Stability-Indicating Analytical Method for Simultaneous Quantification of Metformin Hydrochloride and Empagliflozin by HPTLC |
HPTLC |
Mobile Phase: 2% Ammonium acetate: Isopropyl alcohol: Triethylamine = (4: 6: 0.1 %v/v/v) Stationary phase: Pre-coated silica gel 60 F????? plates (10×10 cm, 0.2 mm) λ max: 242 nm Concentration range: 5000–30,000 ng / band for Metformin 125–750 ng /band for Empagliflozin |
36 |
|
|
31 |
HPTLC – Stability Indicating Densitometric Method for Determination of Metformin Hydrochloride in Tablet Formulation |
HPTLC |
Mobile Phase: water: methanol: triethylamine (1:3.5:0.2 %v/v) Stationary phase: silica gel 60F-254 λ max: 247 nm Concentration range: 100–600 ng /band |
37 |
|
|
32 |
Development and Validation Stability-Indicating HPTLC Method for Determination of Vildagliptin and Metformin Hydrochloride in pharmaceutical dosage forms |
HPTLC |
Mobile Phase: Methanol: Acetonitrile: Glacial Acetic Acid = (2: 3.5: 2.5: 0.2%v/v/v/v) Stationary phase: Pre-coated silica gel 60 F????? HPTLC plate λ max: 217 nm Concentration range: 500 ng/band for Metformin 100 ng/band for Vildagliptin |
38 |
|
|
33 |
Development & Validation of Stability-Indicating HPTLC Method for Metformin Hydrochloride & Benfotiamine in Bulk and Combined Dosage Form |
HPTLC |
Mobile Phase: Benzene: Methanol: Triethylamine = (8.5: 1: 0.5% v/v/v) Stationary phase: Silica gel 60 F????? aluminium TLC-sheet λ max: 249 nm Concentration range: 500–3000 ng / band for Metformin 75-450 ng / band for Benfotiamine |
39 |
|
|
34 |
HPTLC Method for Simultaneous Estimation of Metformin HCl and Sitagliptin in Pharmaceutical Dosage Form |
HPTLC |
Mobile Phase: Ammonium sulphate (0.5%): 2-Propanol: Methanol = (8: 1.6: 1.6%v/v/v) Stationary phase: Pre-coated silica gel 60 F????? plate λ max: 254 nm Concentration range: 7-15μg/spot for Metformin 700-1500 ng/spot for Sitagliptin |
40 |
Literature review of Spironolactone:
Table 2 : Literature review of Spironolactone
|
Sr. No. |
Title |
Method |
Description |
Ref No. |
|
1 |
Zero-order and first-derivative spectrophotometry for the determination of Spironolactone in pharmaceutical tablets |
UV |
Solvent: Methanol λ max: 239 nm (zero-order) & 250.4 nm (1st derivative) Linearity: 6.0-20.0 µg/mL |
41 |
|
2 |
Analysis of spironolactone in compound powder by ultraviolet-visible spectrophotometry
|
UV |
Solvent: Methanol (blank) λ max: 238 nm
Linearity: 5-30 µg/mL |
42 |
|
3 |
Development and validation of combined dosage form of Torsemide and Spironolactone in Ultra-violet spectroscopy by simultaneous equation method |
UV |
Solvent: 50% v/v methanol in distilled water λ max: 288 nm
Linearity: 5-25 µg/mL for Spironolactone, 1-5μg/ml for Torsemide |
43 |
|
4 |
Quantification of Spironolactone by first and second order UV Derivative Spectrophotometry in bulk and tablet dosage form |
UV |
Solvent: Methanol λ max: 226 nm (1st-derivative) & 262 nm (2nd-derivative)
Linearity: 5-35 µg/mL |
44 |
|
5 |
Method development and its validation for estimation of Spironolactone in tablet dosage form by UV spectrophotometry |
UV |
Solvent: 50% v/v methanol in distilled water λ max: 238 nm Linearity: 2-24 µg/mL |
45 |
|
6 |
Simultaneous estimation of Metolazone and Spironolactone in combined tablet dosage form by UV spectroscopy |
UV |
Solvent: 50% v/v methanol in distilled water λ max: 242.5 nm for Spironolactone, 345 nm for Metolazone
Linearity: 5-25μg/ml for Spironolactone,0.5 -2.5μg/ml for Metolazone |
46 |
|
7 |
A New Analytical Method Development and Validation for Quantitative Estimation of Spironolactone and Furosemide in Bulk and Tablet Dosage Form by Using RP-HPLC |
HPLC |
Mobile phase: Methanol: TEA buffer pH 4.2 (40:60% v/v) Stationary phase: Symmetry C18, 4.6 × 150 mm, 5 µm Wavelength: 272 nm Flow rate: 1 ml/min |
47 |
|
8 |
Analytical Method Development and Validation of Spironolactone by RP-HPLC Method |
HPLC |
Mobile phase: 10 mM KH?PO? + 1% TEA (pH 4.5) : Acetonitrile (50:50%v/v) Stationary phase: Hypersil BDS C18, 150 × 4.6 mm, 5 µm Wavelength: 226 nm Flow rate: 1 ml/min |
48 |
|
9 |
Development And Validation of A RP - HPLC Method For The Simultaneous Determination of Spironolactone and Hydrochlorothiazide |
HPLC |
Mobile phase: Methanol: Phosphate buffer pH 4.8 (55:45% v/v) Stationary phase: Inertsil C18, 4.6 × 250mm, 5 µm Wavelength: 282 nm Flow rate: 1 ml/min |
49 |
|
10 |
HPLC – Quality by Design Approach for Simultaneous Detection of Torsemide, Spironolactone and Their Degradant Impurities. |
HPLC |
Mobile phase: Methanol: Acetonitrile: Water (5:3:2% v/v/v) Stationary phase: Inertsil ODS-3 C18 (150×4.6 mm, 3 µm) Wavelength: 254 nm Flow rate: 0.2 ml/min |
50 |
|
11 |
Development and validation of HPTLC and green HPLC methods for determination of furosemide, spironolactone and canrenone, in pure forms, tablets and spiked human plasma |
HPLC |
Mobile phase: Ethanol: Deionized water (45:55% v/v), pH 3.5 Stationary phase: C18 (4.6×100 mm) Wavelength: 254 nm Flow rate: 1 ml/min |
51 |
|
12 |
Development and Validation of High-Performance Liquid Chromatography Assay Method of Spironolactone |
HPLC |
Mobile phase: Phosphate buffer pH 4: Acetonitrile (1:1%v/v) Stationary phase: C18 Inertsil, 250 × 4.6 mm, 5 µm Wavelength: 240 nm Flow rate: 1.5 ml/min |
52 |
|
13 |
Development and Validation of a Stability-Indicating HPLC Assay Method for Simultaneous Determination of Spironolactone and Furosemide |
HPLC |
Mobile phase: Acetonitrile: Ammonium acetate buffer (50:50 %v/v) Stationary phase: Wakosil II 5C8RS, 150 × 4.6 mm, 5 µm Wavelength: 254 nm Flow rate: 1 ml/min |
53 |
|
14 |
Simultaneous Estimation of Furosemide and Spironolactone in Combined Pharmaceutical Dosage Form by RP-HPLC |
HPLC |
Mobile phase: Acetonitrile: Water Stationary phase: Hiber C18, 250 × 4.6mm, 5 µm Wavelength: 237 nm Flow rate: 1 ml/min |
54 |
|
15 |
Stability-Indicating HPTLC Method Development and Validation for Simultaneous Estimation of Spironolactone and Hydrochlorothiazide in Bulk and Tablet |
HPTLC |
Mobile Phase: Methanol: Water = (3:7% v/v) Stationary phase: Silica gel 60 F??? HPTLC plate λ max: 270 nm Concentration range: 100–600 µg/mL for spironolactone 50-300 µg/mL for Hydrochlorothiazide |
55 |
|
16 |
Development and Validation of HPTLC SIAM for Furosemide and Spironolactone |
HPLC |
Mobile Phase: Chloroform: Methanol: Glacial Acetic Acid = (7.5: 2: 0.5% v/v/v) Stationary phase: Silica gel 60 F??? (HPTLC, aluminium) λ max: 234 nm Concentration range: 1000 ng/band for spironolactone 400 ng/band for Furosemide |
56 |
|
17 |
Development and validation of HPTLC and green HPLC methods for determination of furosemide, spironolactone and canrenone, in pure forms, tablets and spiked human plasma
|
HPLC |
Mobile Phase: Ethyl acetate: Triethylamine: Acetic acid = (9: 0.7: 0.5% v/v/v) Stationary phase: Silica gel HPTLC F??? plates λ max: 254 nm Concentration range: 0.05–2.6 µg / band for spironolactone 0.2-2 µg / band for furosemide 0.05-2 µg / band for canrenone |
57 |
|
18 |
Development and Validation of HPTLC Method for Simultaneous Estimation of Metolazone and Spironolactone in Bulk Drug and Pharmaceutical Dosage Form |
HPLC |
Mobile Phase: n-Propanol: Triethylamine = (7: 3 %v/v) Stationary phase: Silica gel 60 F??? (Merck aluminium plate) λ max: 240 nm Concentration range: 300–700 ng / spot for spironolactone 300 -700 ng/spot for Metolazone |
58 |
|
19 |
Development and validation of a HPTLC method for simultaneous determination of furosemide and spironolactone in its tablet formulation |
HPLC |
Mobile Phase: Ethyl acetate: Hexane = (80:20% v/v) Stationary phase: Pre-coated silica gel GF??? (aluminium) λ max: 254 nm Concentration range: 0.040-0.160 mg /ml for spironolactone 0.016-0.064 mg /ml for furosemide |
59 |
CONCLUSION:
Polycystic ovary syndrome (PCOS) is a multifactorial endocrine disorder mainly driven by insulin resistance and hyperandrogenism. Metformin improves insulin sensitivity and metabolic function, while spironolactone effectively reduces androgen-related symptoms. Their combination provides a rational and more effective approach by targeting both metabolic and hormonal abnormalities of PCOS. Clinical evidence supports improved outcomes in terms of body weight, insulin indices, and androgen levels with combination therapy compared to monotherapy. Accurate pharmaceutical analysis is essential for ensuring drug quality and safety. In conclusion, an integrated therapeutic strategy combining metformin and spironolactone, supported by validated analytical methodologies such as RP-HPLC, offers a comprehensive approach to the effective management and pharmaceutical evaluation of PCOS. Continued research focusing on optimized combination therapy and advanced analytical techniques will further enhance treatment outcomes and ensure drug quality, safety, and efficacy in clinical practice.
REFERENCES
Vahoniya Mrunal, Dalwadi Mitali, Chauhan Ajaykumar, A Review of Metformin and Spironolactone in Combined Dosage Form for Polycystic Ovary Syndrome with Emphasis on Pharmaceutical Analysis, Int. J. of Pharm. Sci., 2026, Vol 4, Issue 1, 1924-1938. https://doi.org/10.5281/zenodo.18303725
10.5281/zenodo.18303725
