Figure 1: Chemical structures of EN, LN, AN, and PN

Mini-review:

Table I: Spectrophotometric methods for analysis ofEN, LN, AN, and PN.

Method	Solvent	Linearity (µg/ml)	λ	Application
Direct UV	Methanol: water (10:90)	1-3	224 nm	Determination of EN in tablets [4]
Direct UV	Methanol and water	2-6	277 nm	Determination of EN and LN in tablets [5]
Simultaneous equation	Methanol and water	6-12	277 nm	Determination of EN and LN in tablets [5]
First derivative	Methanol	2.5-30	221 and 238 nm	Determination of EN and LN in tablets [6]
Simultaneous equation	Methanol	2-12	225 and 237 nm	Determination of EN and MN in tablets [7]
PLS-2	Methanol	2-10	200 – 300 nm	Determination of EN and MN in tablets [7]
Simultaneous equation	Methanol	2 - 25	272 and 234 nm	Determination of EN and MN in tablets [8]
Absorption ratio	Methanol	2 - 25	254 and 226 nm	Determination of EN and MN in tablets [8]
First derivative	Methanol	2-12	223.5 and 233.5 nm	Determination of EN and MN in tablets [9]
Direct UV	Water	2 - 12	247 nm	Determination of EN in tablets [10]
Phenanthroline reaction	Water	5 - 30	438 nm	Determination of EN in tablets [10]
K Ferricyanide reaction	Water	10 - 60	782 nm	Determination of EN in tablets [10]
Derivative ratio	Methanol	2 -12	230 and 242 nm	Determination of EN and MN in tablets [11]
Ratio subtraction	Methanol	2 -12	237 nm	Determination of EN and MN in tablets [11]
Ext. ratio subtraction	Methanol	2 -12	225 nm	Determination of EN and MN in tablets [11]
Direct UV	Methanol	5 - 25	296 nm	Determination of LN with EN and MN [12]
Mean centering	Methanol	2 -12	222 and 249 nm	Determination of EN and MN in tablets [13]
First derivative	Methanol	5 - 25	310 nm	Determination of LN with EN and MN [14]
Spectrum subtraction	Methanol	2 -12	225 nm	Determination of EN and MN in tablets [15]
Constant multiplication	Methanol	2 -12	237 nm	Determination of EN and MN in tablets [15]
Direct UV	Methanol and water	5-25	294 nm	Determination of LN in tablets [16]
Direct UV	Methanol and water	10-35	241 nm	Determination of LN in tablets [17]
Direct UV	Methanol	5 - 25	297 nm	Determination of LN in tablets [18]
Simultaneous equation	Methanol	0.5-18	224 nm	Determination of AN and MN in tablets [19]
Absorption ratio	Methanol	0.5-18	251 nm	Determination of AN and MN in tablets [19]
Derivative ratio	Methanol	2.5 - 25	249 and 339 nm	Determination of AN and MN in tablets [20]
Ratio subtraction	Methanol	2.5 - 25	237 nm	Determination of AN and MN in tablets [20]
Ext. ratio subtraction	Methanol	2.5 - 25	277 nm	Determination of AN and MN in tablets [20]
Constant multiplication	Methanol	2.5 - 25	277 nm	Determination of AN and MN in tablets [20]
Spectrum subtraction	Methanol	2.5 - 25	237 nm	Determination of AN and MN in tablets [20]
Direct UV	Methanol	5-35	276nm	Determination of AN in tablets [21]
First derivative	0.1 M Hcl	2 - 16	222 nm	Determination of AN in tablets [22]
Simultaneous equation	Methanol	5 - 25	232 and 277 nm	Determination of AN and MN in tablets [23]
Absorption ratio	Methanol	5 - 25	250 and 277 nm	Determination of AN and MN in tablets [23]
First derivative	Methanol	5 - 30	277 and 268 nm	Determination of AN and PN in tablets [24]
Dual wavelength	Methanol	5 - 30	270 and 265 nm	Determination of AN and PN in tablets [24]
PCR	Acetonitrile	24 - 60	215 and 235 nm	Determination of PN in tablets [25]
PLS	Acetonitrile	24 - 60	215 and 235 nm	Determination of PN in tablets [25]
CLS	Acetonitrile	24 - 60	215 and 235 nm	Determination of PN in tablets [25]
Extractive (ion pair)	Dichloromethane	1 - 65	514 nm	Determination of PN in tablets [26]
Vierodt	0.1 N HCl	2.5 - 25	267 and 269 nm	Determination of PN and sitagliptin in tablets [27]

Table I: Continue………….

Method	Solvent	Linearity (µg/ml)	λ	Application
Multi-wavelength	Acetonitrile: methanol : water (5:4:1)	5 – 50	236.5, 226.4, 227.3 and 254 nm	Determination of PNand MN in tablets [28]
Extractive	Chloroform	2.5 – 14	419 nm	Determination of PN in tablets [29]
Second derivative	Methanol	5 – 25	265.4 nm	Determination of PNand MN in tablets [30]
Absorption correction	Ethanol	3 – 30	268 nm	Determination of PNand MN in tablets [31]
First derivative	Methanol	6 – 30	250 nm	Determination of PN in tablets [32]
Vierodt	Ethanol	3 – 15	210 and 225 nm	Determination of PN in tablets [33]
Vierodt	0.1 N NaOH	5 – 25	216 and 225 nm	Determination of PN in tablets [34]
Direct UV	0.1 M HCl	5 – 30	269 nm	Determination of PN in tablets [35]
Direct UV	Ethanol	5 – 25	224.4 nm	Determination of PN in tablets [36]
Direct UV	0.1 M HCl	10 – 70	269 nm	Determination of PN in tablets [37]
Direct UV	Ethanol:methanol:water	2.5 – 20	267 nm	Determination of PN in tablets [38]
Vierodt	0.1 M NaOH	5 – 25	233 and 265.5 nm	Determination of PNand MN in tablets [39]
Direct UV	Phosphate buffer pH 7.4	10 – 50	238 nm	Determination of PN in tablets [40]
Difference spectrometry	Ethanol and 0.1 M NaOH	5 – 25	225.8	Determination of PN in tablets [41]
Vierodt	Methanol	6 - 14	225 and 237 nm	Determination of PN in tablets [42]

Table II: Chromatographic methods for analysis of EN, LN, AN, and PN.

Stationary phase	Mobile phase	Applications	Detection
C₁₈ column	Phosphate buffer (pH 3): methanol, (30:70 v/v)	Determination of EN in Pharmaceutical dosage form with MN	UV 240 nm [45]
C₁₈ column	Deionized water and acetonitrile in the ratio of (10:90, v/v)	Pharmacokinetic study of EN on human volunteers	MS/MS m/z 449.01to 371.21 [46]
C₁₈ column	Acetonitrile-water(75: 25, v/v)	Determination of EN impurity	MS/MS m/z 785 to m/z 475 [47]
C₁₈ column	Phosphate buffer (pH 4.8), acetonitrile, methanol (15:80:5,v/v/v)	Determination of EN Pharmaceutical dosage form with MN	UV 227 nm [48]
C₁₈ column	0.1% Formic acid: acetonitrile, (50:50, v/v)	Bio-assay of EN in plasma with MN	MS/MS m/z 451.13 to m/z 71.1 [49]
C₈ column	0.1 OPA: Acetonitrile, (70:30, v/v)	Assay of EN in Pharmaceutical dosage form	UV 233 nm [50]
C₁₈ column	Potassium dihydrogen phosphate buffer pH (4)-methanol (50 : 50, v/v)	Assay of EN, LN and MN in tablets	UV 225 nm [51]
C₁₈ column	0.1% aqueous formic acid: acetonitrile, 75:25, v/v	Assay of ENand MN in tablets	MS/MS m/z 451.04 to 71.07 [52]
C₁₈ column	(10 mm sodium dihydrogen phosphate and 10 mm sodium dodecyl sulphate, pH 5.5) and acetonitrile, (64:36 %, v/v).	Stability indicating assay of LN and MN in tablets	UV 208 nm and 228 nm [53]
C₁₈ column	Gradient elution using solvent A: phosphate buffer (pH 3.0) and solvent B: acetonitrile.	Determination of LN and MN in tablets	UV 232 nm [54]
SB-Aq	Gradient elution of KH₂PO₄ buffer solution (0.02M) pH 3.0 adjusted with OPA used as mobile phase-A, and mobile phase-B, ACN:MeOH (90:10, v/v)	Stability indicating assay of LN and MN in tablets	UV 225 nm[55]
C₁₈ column	Mixture of acetonitrile and 0.02M phosphate buffer (pH 5.0) in the ratio of (35:65 %, v/v).	Assay of LN and MN in tablets	UV 225 nm [56]
C₁₈ column	Mixture of phosphate buffer (pH 4.5) and acetonitrile in the ratio of (60:40 %, v/v).	Stability indicating assay of LN and MN in tablets	UV 280 nm [57]
C₁₈ column	Mixture of methanol and 0.05 M potassium dihydrogen orthophosphate (pH 4.6) in the ratio of (70:30 %, v/v).	Assay of LN and MN in tablets	UV 267 nm [58]
silica gel 60 F254	Chloroform: Methanol (8.5:1.5, v/v)	Stability indicating assay of LN in tablets	UV 242 nm [59]
Amylose tris 3,5dimethylphenylcarbamate	Ethanol: Methanol: Monoethanolamine (EtOH:MeOH:MEA) in the ratio of (60:40:0.2, v/v/v)	Stability indicating assay of LN and MN in tablets	UV 225 nm [60]
C₁₈ column	75% methanol: 25% formic acid 0.1% pH 4.1	Pharmacokinetic study of LN in rat plasma	UV 225 nm [61]
C₁₈ column	10 mM Ammonium formate:methanol [20:80 (v/v)]	Bioassay of LN in human plasma	MS/MS m/z 473.3to 420.1 [62]
C₁₈ column	0.01 M Potassium phosphate (pH 4) and acetonitrile in the ratio of (30:70 %, v/v).	Determination of LN in tablets	UV 292 nm [63]

Table II Continue………..

Stationary phase	Mobile phase	Applications	Detection
C₁₈ column	Mixture (pH 4.1) of acetonitrile, water and methanol in the ratio of (25:50:25 %, v/v/v).	Stability indicating assay of LN and MN in tablets	UV 243 nm [64]
Cyano column	Potassium dihydrogen phosphate buffer (pH 4.6) and acetonitrile in the ratio of (20:80 %, v/v).	Determination of LN in tablets	UV 299 nm [65]
C₁₈ column	Mixture (pH 6.4) of acetonitrile, water and methanol in the ratio of (25:50:25 %, v/v/v).	Determination of LN in tablets	UV 238 nm [66]
C₁₈ column	Mixture (pH 3) of water and methanol in the ratio of (60:40 %, v/v).	Determination of LN in tablets	UV 238 nm [67]
C₁₈ column	Methanol and (water containing 0.1% orthophosphoric acid) in the ratio of (70:30 %, v/v) with (pH 6.4).	Determination of LN in tablets	UV 296 nm [68]
C₁₈ column	Phosphate buffer (pH 3), methanol and acetonitrile in the ratio of (45:25:30 %, v/v/v).	Determination of LN and MN in tablets	UV 237 nm [69]
C₁₈ column	Potassium dihydrogen phosphate buffer and acetonitrile in the ratio of (40:60 %, v/v).	Determination of LN and MN in tablets	UV 250nm [70]
C₁₈ column	Phosphate buffer (pH 5.6), methanol and acetonitrile in the ratio of (65:10:25 %, v/v/v).	Determination of LN and MN in tablets	UV 231 nm [71]
C₁₈ column	Methanol and phosphate buffer (pH 4.9) in the ratio of (70:30 %, v/v).	Stability indicating assay of LN in tablets	UV 218 nm [72]
C₁₈ column	Potassium dihydrogen phosphate buffer and acetonitrile in the ratio of (40:60 %, v/v).	Determination of LNand MN in tablets	UV 236 nm [73]
C₁₈ column	Mixture (pH 4.1) of methanol and water in the ratio of (83:17 %, v/v).	Determination of LN in tablets	UV 241 nm [74]
C₁₈ column	Phosphate buffer (pH 3.4) and acetonitrile in the ratio of (70:30 %, v/v)	Determination of LN in tablets	UV 240 nm [75]
C₁₈ column	Phosphate buffer (pH 5.6), methanol and acetonitrile in the ratio of (40:5:55 %, v/v/v).	Determination of LN and MN in tablets	UV 233 nm [76]
C₁₈ column	0.02 M potassium dihydrogen phosphate (pH 5.0) and acetonitrile in the ratio of (70:30 %, v/v).	Determination of LN in tablets	UV 226 nm [77]
C₁₈ column	potassium dihydrogen phosphate buffer pH (4.6) - methanol (30:70, v/v)	Determination of LN and MN in tablets	UV 260 nm [78]
Silica gel 60 F254	Benzene: Ethyl acetate: Triethylamine (7.5: 2: 0.5, v/v/v)	Determination of AN in tablets	UV 222 nm [79]
Silica gel G60-F254	n-butanol : water : acetic acid (6 : 3 :1,v/v/v)	Determination of AN and PN in tablets	UV 270 nm [80]
Cyano column	Mixture of potassium dihydrogen phosphate buffer pH (4.6) and acetonitrile in the ratio of (20:80 %, v/v).	Determination of AN in tablets	UV 215 nm [81]
C₁₈ column	0.2 triethylamine buffer (pH 6.0) and methanol in the ratio of (30:70 %, v/v).	Determination of AN and MN in tablets	UV 254 nm [82]
C₁₈ column	Potassium dihydrogen phosphate buffer (pH 4.0) and acetonitrile in the ratio of (70:30 %, v/v).	Determination of AN and MN in tablets	UV 235 nm [83]
Gold C₁₈ column	Acetonitrile and 0.2 % formic acid aqueous solution as the mobile phase with a gradient elution	Determination of AN and MN in tablets	MS/MS m/z 340.33 to 116.32 [84]
C₁₈ column	Methanol - water (10:90, v/v) at pH 3	Determination of AN and MN in tablets	UV 210 nm [84]
C₁₈ column	Ammonium acetate and methanol (50:50, v/v)	Determination of AN and PN in tablets	UV 248 nm [85]
C₁₈ column	Gradient elution of (0.1% perchloric acid pH 3 - acetonitrile in the ratio of 90:10, v/v) and (0.1% perchloric acid pH 3 - acetonitrile in the ratio of 40:60 %, v/v)	Characterization of process-related impurities including forced degradation products of AN	UV 224 nm [86]
C₁₈ column	Mixture of phosphate buffer and acetonitrile in ratio of (45:55 %, v/v)	Stability indicating assay of AN and PN in tablets	UV 215 nm [87]
C₁₈ column	Mixture (pH 6.8) of methanol and double distilled water in the ratio of (80:20 %, v/v)	Determination of AN in tablets	UV 222 nm [88]
Gold C₁₈ column	Gradient elution of acetonitrile and 0.2% formic acid solution	Pharmacokinetic study of AN and MN in human plasma	MS/MS m/z 340.33 to 116.32 [89]
C₈ column	Acetonitrile-10 mM ammonium acetate buffer (pH 3.5; 90 + 10, v/v)	Stability indicating assay of AN in tablets	UV 275 nm [90]
C₁₈ column	Phosphate buffer (pH 3.5) and methanol in the ratio of (70:30 %, v/v).	Determination of AN and PN in tablets	UV 271 nm [91]

Table II Continue………..

Stationary phase	Mobile phase	Applications	Detection
C₁₈ column	Phosphate buffer (pH 3.6) and acetonitrile in the ratio of (35:65 %, v/v).	Determination of AN and PN in tablets	UV 268 nm [92]
C₁₈ column	Potassium dihydrogen phosphate buffer (pH 3), methanol and acetonitrile in the ratio of (20:60:20 %, v/v/v).	Determination of AN and MN in tablets	UV 290 nm [93]
C₁₈ column	Phosphate buffer (pH 4.8) and acetonitrile in the ratio of (48:52 %, v/v).	Determination of AN and MN in tablets	UV 210 nm [94]
C₁₈ column	Methanol and phosphate buffer (pH 3) in the ratio of (80:20 %, v/v).	Determination of AN and PN in tablets	UV 269 nm [95]
Silica gel 60F254	n-butanol:water:acetic acid (7:2:1,v/v/v)	Stability indicating assay of AN in tablets	UV 233 nm [96]
Silica gel 60F254	Chloroform-methanol-ethyl acetate-triethyl amine, 9+1+1+0.5, v/v/v/v	Stability indicating assay of AN in tablets	UV 278 nm [97]
C₁₈ column	0.2% formic acid-0.2% ammonium acetate in water as mobile phase A, acetonitrile and methanol (60:40, v/v) as mobile phase B in linear gradient elution mode	Characterization of related impurities of AN	MS/MS m/z 323.1507 to 266.1296 [98]
C₁₈ column	Water and methanol as 75:25, (v/v)	Determination of AN in tablets	UV 278 nm [99]
C₁₈column	The mobile phase A is 0.1% w/vtriethylamine in water with pH 2.5 adjusted by dilute phosphoric acid. The mobile phase B is premixed and degassed mixtures of acetonitrile and methanol in gradient mode.	Determination of related substances of PN	UV 225 nm [100]
Cyano column	Isocratic elutionmode with a mobile phase of acetonitrile: 0.02 M potassium dihydrogen phosphate (pH 3.17;50–50, v/v)	Determination of PN and MN in the Presence of metformin impurity (1 -Cyanoguanidine)	UV 220 nm [101]
High-purity silica column	Mixture of methanoland 10mM phosphate buffer (pH 3.0) (94:6, v/v)	Determination of PN and MN in rabbit plasma	UV 230 nm [102]
C₁₈column	Mixture of acetonitrile and ammonium acetate buffer (pH 5.0) as mobile phase in ratio 60 : 40 (v/v)	Determination of PN in tablets	UV 270 nm [103]
C₁₈column	Mixture of Buffer (0.05 M potassium dihydrogen phosphate and pH adjusted to 3.1 with orthophosphoric acid) and Acetronitrile in a ratio of (40:60, v/v)	Stability indicating determination of PN in tablets	UV 226 nm [104]
C₁₈column	Isocratic elution using mixture of solvent A: ammonium acetate buffer and acetonitrile in the ratio of (57:43, v/v) and solvent B: ammonium acetate buffer and acetonitrile in the ratio of (20:80, v/v)	Stability indicating determination of PN in tablets	UV 254 nm [105]
C₁₈column	Mixture of (50:50) methanol: phosphate buffer, pH 6.5 containing 0.01 M sodium dodecyl sulphate	Stability indicating determination of PN and MN in tablets	UV 270 nm [106]
C₁₈column	Mixture ofmethanol: pH4.6 buffer (80:20 %v/v) adjusted to pH 4.6 with 0.1 % v/v glacial acetic acid	Determination of PN in tablets	UV 273 nm [107]
C₁₈column	Mixture of methanol–water (90 + 10, v/v), with pH adjusted to3.50 with phosphoric acid.	Determination of PN in tablets	UV 235 nm [108]
C₁₈column	Mixture of phosphate buffer [pH: 4]:methanol:acetonitrile: triethylamine[40:20:40:0.1, v/v/v/v]	Determination of PN with glimepiride in tablets	UV 228 nm [109]
C₁₈column	Phosphate buffer pH (3.5), methanol and acetonitrile in the ratio of (70:20:10, v/v/v)	Determination of PN with AN and MN in tablets	UV 220 nm [110]
C₁₈ column	Potassium dihydrogen phosphate buffer pH (4.6)-acetonitrile (60:40, v/v)	Determination of PN and MN in tablets	UV 210 nm [111]
C₁₈column	MP-A; 0.05 M phosphate buffer (pH 6.0) methanol(9:1, v/v)	Determination of PN in plasma	UV 269 nm [112]
C₁₈column	Methanol:ACN:phosphatebuffer (pH 2.6; 0.01 M), (40:12:48, v/v/v)	Determination of PN in plasma	UV 269 nm [113]
C₁₈column	methanol: 5 mM ammoniumacetate in 0.1% formic acid (80:20, v/v)	Determination of PN in plasma in the presence of its metabolite	MS/MS m/z 357.1 to 134.0 [114]
C₁₈column	0.05 M ammonium acetate(pH 4.6) and acetonitrile(20/80, v/v)	Determination of PN in urine	UV 270 nm [115]

Table II Continue………..

Stationary phase	Mobile phase	Applications	Detection
C₁₈column	Methanol and ammoniumacetate (0.03 M;pH 5) (60:40, v/v).	Determination of PN in plasma	UV 269 nm [116]
C₁₈column	Methanol and ammoniumacetate buffer (pH 3.5) (55:45)	Determination of PN in plasma	UV 252 nm [117]
POLAR-RP 80A	Acetonitrile–water with 6 mM ammonium acetate and 0.1%formic acid (50:50, v/v)	Determination of PNand MN in dog plasma	MS/MS m/z 357.1 to 134.0 [118]
Gold C₁₈column	The mobile phase was made of deion-ized water and acetonitrile, both of which contained 0.2% formicacid and 5 mM ammonium acetate. A gradient system was set tostart with the ratio of deionized water:acetonitrile at 80:20 fromtime 0 to 0.5 min.	Determination of PN in plasma in the presence of its metabolite	MS/MS m/z 356.8 to 133.9 [119]
C₁₈column	Phosphate buffer (pH 2.6;0.01 M):methanol:ACN:perchloric acid	Determination of PN in plasma	UV 269 nm [120]
C₁₈column	Methanol–water–acetonitrile(80:10:10, v/v/v)	Determination of PN in plasma	UV 230 nm [121]
C₈column	Phosphate buffer (pH 4.0), ACN andmethanol (55:30:15, v/v)	Determination of PN in tablets	UV 245 nm [122]
C₁₈column	0.01 M potassium dihydrogen phosphatebuffer (pH 3.5):methanol (55:45, v/v)	Stability indicating Determination of PN in tablets	UV 241 nm [123]
Silica gel 60 F254	Mixture of toluene, ethyl acetate, methanol and glacial acetic acid at a ratio of 70:15:10:5,v/v/v/v	Determination of PN and Glimepiride in tablets	UV 235 nm [124]
Silica gel 60 aluminum sheets	Chloroform–methanol (10:1,v/v)	Determination of PN in tablets	UV 254 nm [125]
C₁₈column	80:20 (v/v) mixture of acetonitrile and 0.1% formic acid	Pharmacokinetic study of PN and candesartan in human plasma	MS/MS m/z 357.1 to 134.0 [126]
C₁₈column	Ammonium formate buffer (pH 3):CAN (75:25, v/v)	Determination of PN in tablets	UV 225 nm [127]
C₁₈column	Ammonium formate buffer (pH 4.1):CAN (44:55, v/v)	Determination of PN in tablets	UV 266 nm [128]
C₈column	ACN:(0.15, v/v) triethylamine (pH 4.6)(40:60, v/v)	Determination of PN in tablets	UV 220 nm [129]
C₁₈column	0.01 M triammonium citrate (pH 6.95): ACN: methanol (45:35:20, v/v/v)	Determination of PNand Glimepiride in tablets	UV 228 nm [130]
C₁₈column	ACN:potassium dihydrogen phosphatebuffer (pH 3 ) (50:50, v/v)	Determination of PN and MN in tablets	UV 238 nm [131]
Silica gel 60 F254	acetonitrile,methanol, propyl alcohol, and ammonium acetate solutions in theproportion of 7:2:1:1 (v/v)	Determination of PN, MNand Glimepiride in tablets	UV 240 nm [132]
C₁₈column	ACN:0.05 M potassium dihydrogenorthophosphate buffer of pH 3.0 (50:50, v/v)	Determination of PN and its impurities in tablets	UV 225 nm [133]
C₁₈column	ACN:0.02 M ammonium acetate (pH 4.5), (60:40, v/v)	Determination of PN and Glimepiride in tablets	UV 230 nm [134]
C₁₈column	Methanol:phosphate buffer (pH 4.3) (75:25, v/v)	Determination of PN, MN and Glimepiride in tablets	UV 258 nm [135]
C₁₈column	Acetonitrile:water (60:40) with 10 mMammonium acetate and 0.02% TFA	Determination of PN in plasma in the presence of its metabolite	MS/MS m/z 357.0 to 134.0 [136]
CN F254	1,4-dioxane - pH 4.4 buffer (5 : 5)	Determination of PN in tablets	UV 266 nm [137]
C₁₈column	ACN:phosphate buffer (pH 7) (60:40, v/v)	Determination of PN and saxagliptin in tablets	UV 260 nm [138]
C₁₈column	ACN:0.01 M potassium dihydrogenorthophosphate (pH 6.2) (50:50, v/v)	Determination of PN and Glimepiride in tablets	UV 225 nm [139]
C₁₈column	Dil. orthophosphoric acid (pH 3.0):CAN (80:20, v/v)	Determination of PN and Glimepiride in tablets	UV 215 nm [140]
C₁₈column	100% aqueous loading mobile phase containing 5 mM ammonium acetate (pH 4.0)	Determination of PN in human serum	MS/MS m/z 357.0 to 134.0 [141]
C₁₈column	ACN:water:acetic acid (75:25:0.3, v/v/v), pH 5.5	Determination of PN and MN in tablets	UV 230 nm [142]

Table II Continue………..

Stationary phase	Mobile phase	Applications	Detection
C₁₈column	Phosphate buffer: ACN:tetrahydrofuran(40:50:10, v/v/v)	Determination of PN, MN and Glimepiride in tablets	UV 228 nm [143]
C₁₈column	Phosphate buffer: ACN (40:60, v/v)	Determination of PN and Glimepiride in tablets	UV 225 nm [144]
Cyanocolumn	Solution-A is 0.02 M potassium dihydrogenphosphate, pH 3.2. Solution-B is ACN	Determination of PN and Glimepiride in tablets	UV 230 nm [145]
C₁₈column	Methanol:0.02 M potassium dihydrogenphosphate (85:15, v/v)	Determination of PN and MN in tablets	UV 227 nm [146]
C₁₈column	Methanol:water (72:28, v/v)	Determination of PN and Glimepiride in tablets	UV 230 nm [147]
C₈column	ACN:ammonium dihydrogen phosphate (pH4.5; 0.02 M) (65:35, v/v)	Determination of PNand telmisartan in tablets	UV 210 nm [148]
C₁₈column	ACN:phosphate buffer (pH 3) (65:35, v/v)	Determination of PN, MN and Glimepiride in tablets	UV 245 nm [149]
C₁₈column	Tween-20: n-butanol: phosphate buffer, (pH4.2) (50:25:25,v/v/v)	Determination of PN in tablets	UV 322 nm [150]
C₁₈column	Sol-A: phosphate buffer pH 3.1 and Sol-B:acetonitrile	Determination of PN and its impurities in tablets	UV 225 nm [151]
C₁₈column	0.01 M buffer:methanol (40:60, v/v)	Determination of PN in tablets	UV240 nm [152]

REFERENCES:

1. Hansen, H.H., Jelsing, J., Hansen, C.F., Hansen, G., Vrang, N., Mark, M., Klein, T., Mayoux, E. The sodium glucose co transporter type 2 inhibitor empagliflozin preserves β-cell mass and restores glucose homeostasis in the male zucker diabetic fatty rat. (2014) The Journal of pharmacology and experimental therapeutics, 350 (3), pp. 657-664.

2. Baetta, R., Corsini, A. Pharmacology of dipeptidyl peptidase-4 inhibitors: Similarities and differences (2011) Drugs, 71 (11), pp. 1441-1467.

3. New Insulin Sensitizers for the Treatment of Type 2 Diabetes (2012) Annual Reports in Medicinal Chemistry, 47, pp. 177-192.

4. Sushil D. Patil, Sayali K. Chaure, Maswood Ahmed Hafizur Rahman, Prajkta U. Varpe, Sanjay Kshirsagar.. Development and Validation of Simple UV- Spectrophotometric Method for the Determination of Empagliflozin. Asian J. Pharm. Ana. 2017; 7(1): 18-22.

5. Padmaja N., Veerabhadram G. Development and validation of analytical method for Simultaneous estimation of Empagliflozin and Linagliptin in bulk drugs and combined dosage forms using UV-visible spectroscopy (2015) Der Pharmacia Lettre, 7 (12), pp. 306-312.

6. Amrutiya, F.R., Patel, B.R., Patel, J.G., Vegad, K.L., Patel, A.S., Darji, V.C. Development and validation of first order derivative UV spectrophotometric method for determination of empagliflozin and linagliptin (2017) Int. J. Pharm. Drug Anal., 5 (4): 129-135.

7. Ayoub B.M. Development and validation of simple spectrophotometric and chemometric methods for simultaneous determination of empagliflozin and metformin: Applied to recently approved pharmaceutical formulation (2016) Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 168, pp. 118-122.

8. Padmaja, N., Babu, M.S., Veerabhadram, G. Development and validation of UV spectrophotometric method for Simultaneous estimation of Empagliflozin and Metformin hydrochloride in bulk drugs and combined dosage forms (2016) Der Pharmacia Lettre, 8 (13), pp. 207-213.

9. Ayoub B.M. Application of spiking technique coupled with derivative spectrophotometry for the analysis of a novel anti-diabetic combination of two coformulated drugs with highly different concentrations (2016) Der Pharma Chemica, 8 (10), pp. 12-14.

10. Jyothirmai, N., Nagaraju, B., Anil, K.M. Novel UV and Visible Spectrophotometric methods for the analysis of Empagliflozin a type 2 diabetic drug in bulk and pharmaceutical formulations (2016) Journal De Afrikana, 3 (1), pp. 177-187.

11. Ayoub B.M. Green pharmaceutical analysis of drugs coformulated with highly different concentrations using spiking and manipulation of their ratio spectra (2017) Journal of AOAC International, 100 (4), pp. 985-991.

12. Shaker L. Development of economic UV spectrophotometric method for determination of linagliptin in its ternary mixture with empagliflozin and metformin: Comparison to economic pharmaceutical analysis in literature (2016) Der Pharmacia Lettre, 8 (13), pp. 267-269.

13. Ayoub B.M., Emam R.M., Youssef M.M., El-Kattan M.N., Sayed M.A., Kowider A.M., Seha A.H., Rabea E.A., Yakout R.M., Faried R.H. Mean centering method for determination of empagliflozin and metformin (2017) Marmara Pharmaceutical Journal, 21 (3), pp. 669-674.

14. Shaker L. A new cost effective first derivative spectrophotometric method for assay of linagliptin in combination with selected antidiabetics: Compared to previously reported cost effective procedures (2016) Der Pharmacia Lettre, 8 (13), pp. 256-258.

15. Ayoub B.M. Quantitative analysis of drugs with highly different concentrations of pharmaceutical components using the techniques of spectrum subtraction (2017) Journal of Analytical Chemistry, 72 (9), Article in press.

16. Banik S., Karmakar P., Miah MD. Development and Validation of a UV-Spectrophotometric Method for Determination of Vildagliptin and Linagliptin in Bulk and Pharmaceutical Dosage Forms (2015) Bangladesh Pharmaceutical Journal, 18(2), pp. 163-168.

17. Sekhar C.K., Sudhakar P., Rao T.M., Babu P.V., Manikanta K.A. A New Uv-Method for Determination of Linagliptin in Bulk and Pharmaceutical Dosage Form (2013) International Journal of Universal Pharmacy and Bio Sciences, 2(4), pp. 1-6.

18. Zalte, A.G., Saudagar, R.B., Katkade, P.N. Validated UV- spectroscopic estimation of Linagliptin concentration in bulk and dosage form (2016) Research Journal of Pharmacy and Technology, 9 (5), pp. 490-492.

19. Sen D.B., Sen A.K., Zanwar A., Balaraman R., Seth A.K. Determination of alogliptin benzoate and metformin hydrochloride in tablet dosage form by simultaneous equation and absorption ratio method (2015) International Journal of Pharmacy and Pharmaceutical Sciences, 7 (8), pp. 380-383.

20. Zaghary, W.A., Mowaka, S., Hassan, M.A., Ayoub, B.M. Comparative study between different simple methods manipulating ratio spectra for the analysis of alogliptin and metformin co-formulated with highly different concentrations (2017) Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 186, pp. 23-28.

21. Supriya P., Madhavi Latha N., Rohith K.B.V., Ramana G.V., Harini U., Pawar A.K.M. Development and validation of uv spectrophotometric and reversed phase-high performance liquid chromatography - PDA methods for the estimation of alogliptin benzoate (2016) Asian Journal of Pharmaceutical and Clinical Research, 9 (1), pp. 264-269.

22. Yadav P. J., Kadam V.N., Mohite S.K. Development and Validation of UV Spectrophotometric Method for Alogliptin Benzoate in Bulk Drug and Tablet Formulation (2014) Journal of Current Pharma Research, 4(4), pp. 1286-1290.

23. Chirag, Parle A. Development and validation of UV spectrophotometric method for simultaneous estimation of metformin hydrochloride and alogliptin benzoate in bulk drugs and combined dosage forms (2014) Der Pharma Chemica, 6 (1), pp. 303-311.

24. Kashyap R., Srinivasa U. First order derivative and dual wavelength spectrophotometry methods development and validation for simultaneous estimation of Alogliptin and Pioglitazone in bulk and dosage form (2014) International Journal of Pharmacy and Pharmaceutical Sciences, 6 (SUPPL. 2), pp. 730-738.

25. El-Zaher A.A., Elkady E.F., Elwy H.M., Saleh M.A.E.M. Simultaneous spectrophotometric determination of glimepiride and pioglitazone in binary mixture and combined dosage form using chemometric-assisted techniques (2017) Spectrochimica Acta - Part A: Molecular and Biomolecular Spectroscopy, 182, pp. 175-182.

26. Okdeh M., Sakur A.A., Alfares B. Determination of pioglitazone in bulk and pharmaceutical formulations by extractive spectrophotometric method using ion - pair formation (2014) International Journal of Pharmacy and Pharmaceutical Sciences, 6 (5), pp. 43-47.

27. S.S. Kumar, Y. Krishnaveni, G. Ramesh, Simultaneous estimation ofsitagliptin and pioglitazone by UV-spectroscopic method and study of interference of various excipients on this combination of drugs, Int. J. Curr. Pharm. Res. 4 (2012) 113–116.

28. L. Adhikari, S. Jagadev, S. Sahoo, et al., Devlopement and validationof UV–visible spectrophotometric method for simultaneous determi-nation of pioglitazone HCl, metformin HCl and glipizide in its bulkand pharmaceutical dosage form (tablet), Int. J. ChemTech Res. 4(2012) 625–630.

29. M. Amanlou, M. Zarei-Ghobadi, M.K. Rofouei, et al., Extractive spectrophotometric method for determination of pioglitazone HCl inraw material and tablets using ion-pair formation, J. Chem. 7 (2010)915–921.

30. P. Deepa, P. Laxmanbhai, P. Madhabhai, et al., Simultaneous estimation of glimepiride, pioglitazone HCl and metformin HCl by derivative spectrophotometry method, Int. Res. J. Pharm. 2 (2011)111–114.

31. S.M. Dhole, P.B. Khedekar, N.D. Amnerkar, UV spectrophotometric absorption correction method for the simultaneous estimation of pioglitazone HCl, metformin HCl and glibenclamide in multicompo-nent formulation, Int. J. Anal. Bioanal. Chem. 3 (2013) 18–22.

32. M.D. Game, First order derivative spectrophotometric method for simultaneous estimation of glimepiride and pioglitazone HCl incombined dosage form, J. Pharm. Res. 4 (2011) 4301–4302.

33. O.S. Havele, S.S. Havele, Simultaneous determination of atorvastatincalcium and pioglitazone hydrochloride in its multicomponent dosage forms by UV spectrophotometry, Int. J. Pharm. Sci. Res. 1 (2011) 75–79.

34. L. Kishore, N. Kaur, Estimation of pioglitazone and glimipride in its pharmaceutical dosage form by spectrophotometric methods, DerPharm. Lett. 3 (2011) 276–284.

35. S.P. Mahadik, G.P. Senthilkumar, Method development and validation of pioglitazone in bulk and pharmaceutical dosage forms by using spectrophotometric method, Asian J. Biochem. Pharm. Res. 2 (2012)159–165.

36. M. Younus Ali, P.V. Swamy, P. Borgaonkar, et al., UV-spectro-photometric determination of pioglitazone in pharmaceutical dosage forms, Int. J. Chem. Sci. 6 (2008) 2062–2065.

37. S. Mohd, A.P. Kulkarni, Z. Zaheer, et al., Spectroscopic estimation of pioglitazone hydrochloride, Int. J. Pharm. Frontier Res. 2 (2012) 87–94.

38. S. Patil, S. Dwivedi, S. Bagade, Development of spectrophotometric method for the estimation of pioglitazone HCl from two different marketed brands, Am. J. Pharm Tech Res. 1 (2011) 264–275.

39. S.D. Rathod, P.M. Patil, S.B. Jadhav, et al., UV-spectrophotometric simultaneous determination of metformin HCl and pioglitazone HClin combined dosage form, Asian J. Pharm. Anal. 2 (2012) 05–09.

40. P. Shakya, K. Singh, Determination of pioglitazone hydrochloride inbulk and pharmaceutical formulations by UV spectrophotometric method, Int. J. Pharm. Sci. Res. 1 (2010) 153–157.

41. K. Sujana, K. Abbulu, O.B. Souri, et al., Difference spectrophoto-metric methods for pioglitazone HCl and metformin HCl, J. Pharm.Sci. Res. 3 (2011) 1122–1126.

42. K. Sujana, G.S. Rani, M.B. Prasad, et al., Simultaneous estimation of pioglitazone HCl and metformin HCl using UV spectroscopic method, J. Biomed. Sci. Res. 2 (2010) 110–115.

43. Ayoub, B.M. Linagliptin: A concise review on analytical and bio-analytical methods (2016) Der Pharma Chemica, 8 (9), pp. 23-29.

44. Ayoub, B.M. Mini-review: Analytical procedures for alogliptin determination in biological fluids and pharmaceutical formulations (2016) Der Pharma Chemica, 8 (9), pp. 18-22.

45. Madana Gopal, N., Sridhar, C. A validated stability indicating ultra-performance liquid chromatographic method for simultaneous determination of metformin hydrochloride and empagliflozin in bulk drug and tablet dosage form (2017) International Journal of Applied Pharmaceutics, 9 (3), pp. 45-50.

46. Ayoub, B.M., Mowaka, S., Elzanfaly, E.S., Ashoush, N., Elmazar, M.M., Mousa, S.A. Pharmacokinetic Evaluation of Empagliflozin in Healthy Egyptian Volunteers Using LC-MS/MS and Comparison with Other Ethnic Populations (2017) Scientific Reports, 7 (1), art. No. 2583.

47. Zhou, H., Meng, F.-H., Sun, L., Qiao, S.-Y., Zhang, G.-G. Related substances in empagliflozin determined by LC-MS/MS (2016) Journal of International Pharmaceutical Research, 43 (4), pp. 753-756.

48. Geetha Swarupa, P., Lakshmana Rao, K., Prasad, K.R.S., Suresh Babu, K. Development and validation of stability indicating reversed phase high-pressure liquid chromatography method for simultaneous estimation of metformin and empagliflozin in bulk and tablet dosage form (2016) Asian Journal of Pharmaceutical and Clinical Research, 9, pp. 126-135.

49. Ayoub, B.M. Enhancement of plasma extraction recovery of empagliflozin and metformin combination using liquid-liquid extraction and vacuum evaporation techniques (2016) Der Pharma Chemica, 8 (10), pp. 163-166.

50. Shyamala, Nirmala, K., Mounika, J., Nandini, B. Validated stability-indicating RP-HPLC method for determination of Empagliflozin (2016) Der Pharmacia Lettre, 8 (2), pp. 457-464.

51. Ayoub, B.M. UPLC simultaneous determination of empagliflozin, linagliptin and metformin (2015) RSC Advances, 5 (116), pp. 95703-95709.

52. Ayoub, B.M., Mowaka, S. LC-MS/MS determination of empagliflozin and metformin (2017) Journal of Chromatographic Science, 55 (7), pp. 742-747.

53. Attimarad M., Nagaraja S.H., Aldhubaib B.E., Nair A., Venugopala K.N. Simultaneous determination of metformin and three gliptins in pharmaceutical formulations using RP HPLC: Application to stability studies on Linagliptin tablet formulation (2014) Indian Journal of Pharmaceutical Education and Research, 48 (4), pp. 45-53.

54. Pednekar S., Lokhande R., Sutar R., Kolhal S., Surve S., Gudekar S. Simultaneous determination of metformin, Sitagliptin, Saxagliptin, Linagliptin and vildagliptin in multicomponent pharmaceutical preparations by RP-HPLC (2014) International Journal of Pharmaceutical Sciences Review and Research, 28 (1), art. No. 24, pp. 128-133.

55. Jadhav, S.B., Reddy, P.S., Narayanan, K.L., Bhosale, P.N. Development of RP-HPLC, stability indicating method for degradation products of linagliptin in presence of metformin HCL by applying 2 level factorial design; and identification of impurity-VII, VIII and IX and synthesis of impurity-VII (2017) Scientia Pharmaceutica, 85 (3), art. No. 25.

56. Varaprasad C., Asif M., Ramakrishna K. RP-HPLC method for simultaneous estimation of metformin and linagliptin in tablet dosage form (2015) Rasayan Journal of Chemistry, 8 (4), pp. 426-432.

57. Mallikarjuna Rao N., Gowri Sankar D. RP-HPLC method for simultaneous estimation and stability indicating study of metformin and linagliptin in pure and pharmaceutical dosage forms (2015) International Journal of Pharmacy and Pharmaceutical Sciences, 7 (3), pp. 191-197.

58. Vemula P., Dodda D., Balekari U., Panga S., Veeresham C. Simultaneous determination of linagliptin and metformin by reverse phase-high performance liquid chromatography method: An application in quantitative analysis of pharmaceutical dosage forms (2015) Journal of Advanced Pharmaceutical Technology and Research, 6 (1), pp. 25-28.

59. Butle, S.R., Deshpande, P.B. Application of accelerated stability studies on linagliptin by HPTLC (2017) Asian Journal of Chemistry, 29 (1), pp. 94-98.

60. Jadhav, S.B., Mane, R.M., Narayanan, K.L., Bhosale, P.N. Analytical enantio-separation of linagliptin in linagliptin and metformin HCl dosage forms by applying two-level factorial design (2016) Scientia Pharmaceutica, 84 (4), art. No. 84, pp. 671-684.

61. Hanafy, A., Mahgoub, H. A Validated HPLC Method for the Determination of Linagliptin in Rat Plasma. Application to a Pharmacokinetic Study (2016) Journal of Chromatographic Science, 54 (9), pp. 1573-1577.

62. Nannapaneni, N.K., Jalalpure, S.S., Muppavarapu, R., Sirigiri, S.K. An ultra high performance liquid chromatography-tandem mass spectrometry method for the quantification of linagliptin in human plasma (2016) RSC Advances, 6 (71), pp. 66756-66766.

63. Dubey N., Singh G.N., Tyagi A., Bhardwaj R., Raghav C.S. Development and validation of ultra-performance liquid chromatography (UP-LC) method for estimation of a new anti-diabetic drug linagliptin in bulk and its tablet formulation (2014) Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 53 (8), pp. 1136-1139.

64. Kavitha K.Y., Geetha G., Hariprasad R., Kaviarasu M., Venkatnarayanan R. Development and validation of stability indicating RP-HPLC method for the simultaneous estimation of linagliptin and metformin in pure and pharmaceutical dosage form (2013) Journal of Chemical and Pharmaceutical Research, 5 (1), pp. 230-235.

65. El-Bagary R.I., Elkady E.F., Ayoub B.M. Liquid chromatographic determination of linagliptin in bulk, in plasma and in its pharmaceutical preparation (2012) International Journal of Biomedical Science, 8 (3), pp. 209-214.

66. Lakshmi B., Reddy T.V. A novel RP-HPLC method for the quantification of linagliptin in formulations (2012) Journal of atoms and molecules, 2 (2), pp. 155-164.

67. Patil D.A., Patil V.A., Bari S.B. Development and validation of RP-HPLC method for the analysis of linagliptin (2012) Inventi rapid-Pharm analysis and quality assurance, 12 (1), pp. 598-603.

68. Sri V.K., Anusha M., Reddy S.R. A Rapid RP-HPLC Method development and Validation for the Analysis of Linagliptinin Bulk and Pharmaceutical Dosage Form (2015) Asian Journal of Pharmaceutical Analysis, 5(1), pp. 6-20.

69. Prasanna A.C., Pavani S., Priyanka K. Method development and validation of linagliptin and metformin by using RP-HPLC in pharmaceutical dosage form (2015) International Journal of Advances in Pharmaceutical Sciences, 6(1), pp. 2673-2678.

70. Shirisha S., Haque M.A., Sireesha D., Bakshi V., Harshini S. Development and validation of RP-HPLC method for simultaneous estimation of metformin and linagliptin in combined pharmaceutical dosage form (2015) International Journal of Pharma Research and Health Sciences, 2(6), pp. 491-495.

71. Moncy S., Reddy G.R., Reddy P.S., Priyanka G., Bindu E.H. Simultaneous determination of metformin hydrochloride and linagliptin by RP-HPLC in bulk and pharmaceutical formulations (2014) Indo American Journal of Pharmaceutical Research, 4(10), pp. 4047-4053.

72. Reddy B.S., Rao N.V.B., Saraswathi K. A validated stability-indicating HPLC assay method for linagliptin (2014) Der Pharmacia Sinica, 5(5), pp. 131-137.

73. Varma A.R., Shanmukhakumar J.V., Reddy S.M. Stability indicating liquid chromatographic method for the simultaneous assay of anti-diabetic drugs, linagliptin and metformin, in pure and in their commercial tablet dosage form (2014) International Journal of Innovative Technology and Research, 2(4), pp. 1131–1138.

74. Badugu L.R. A Validated RP-HPLC Method for the Determination of Linagliptin (2014) American Journal of Pharmatech Research, 2(4) pp. 462-470.

75. Sujatha K., Rao J.S. A new RP-HPLC method for the estimation of linagliptin in tablet dosage forms (2013) Indo American Journal of Pharmaceutical Research, 3(10), pp. 8346-8381.

76. Swamy A.J., Baba K.H. Analytical Method development and Method validation for the simultaneous estimation of Metformin HCL and Linagliptin in Bulk and tablet Dosage Form by RP-HPLC Method (2013) International Journal of Pharmacy, 3(3), pp. 594-600.

77. Archana M., Sriram N., Gayasuddin M. Method development and validation of RP-HPLC method for determination of new antidiabetic agent linagliptin in bulk and in pharmaceutical formulation (2013) International Journal of Medicinal Chemistry and Analysis, 3(1), pp. 1-5.

78. El-Bagary R.I., Elkady E.F., Ayoub B.M. Spectrophotometric methods for the determination of linagliptin in binary mixture with metformin hydrochloride and simultaneous determination of linagliptin and metformin hydrochloride using high performance liquid chromatography (2013) International Journal of Biomedical Science, 9 (1), pp. 41-47.

79. Deshpande, P.B., Butle, S.R. Stability indicating high performance thin layer chromatographic determination of Alogliptin Benzoate as bulk drug and in tablet dosage form (2017) Eurasian Journal of Analytical Chemistry, 12 (4), pp. 325-335.

80. Shah, D.A., Gajjar, U., Mehta, F.A., Patel, V.B., Chhalotiya, U.K. Development of HPTLC method for the estimation of Pioglitazone and Alogliptin in synthetic mixture (2017) Indian Drugs, 54 (2), pp. 44-52.

81. El-Bagary R.I., Elkady F.E., Ayoub B.M. Liquid Chromatographic Determination of Alogliptin in Bulk and in its Pharmaceutical Preparation (2012) International journal of Biomedical science, 8 (3), pp. 215-218.

82. Kumar A.P., Aruna G., Rajasekar K., Reddy P.J. Analytical method development and validation of alogliptin and metformin hydrochloride tablet dosage form by RP-HPLC method (2013) International Bulletin of Drug Research, 3(5), pp. 58-68.

83. Sri G.S., Kumar S.A., Saravanan J., Debnath M, Greeshma V. KrishnaN.S. A new rp-hplc method development for simultaneous estimation of metformin and alogliptin in bulk as well as in pharmaceutical formulation by using PDA detector (2013) World Journal of Pharmacy and Pharmaceutical Sciences, 2 (6), pp. 6720-6743.

84. Mowaka, S., Ayoub, B.M. Comparative study between UHPLC-UV and UPLC-MS/MS methods for determination of alogliptin and metformin in their pharmaceutical combination (2017) Pharmazie, 72 (2), pp. 67-72.

85. Haribabu, B., Rama Krishna Veni, P., Bala Murali Krishna, K., Lakshmi Prameela, K. RP-HPLC estimation of alogliptin and pioglitazone simultaneously in combined tablet dosage forms (2017) Marmara Pharmaceutical Journal, 21 (2), 10.

86. Zhou Y., Zhou W., Sun L., Zou Q., Wei P., OuYang P. Characterization of process-related impurities including forced degradation products of alogliptin benzoate and the development of the corresponding reversed-phase high-performance liquid chromatography method (2014) Journal of Separation Science, 37, pp. 1248–1255.

87. Neelima B., Kumar P. R, Bindu V.H., Prasad Y.R. A validated stability indicating RP-HPLC method for simultaneous determination of alogliptine and pioglitazone in bulk and pharmaceutical formulations (2014) International Journal of Pharmacy, 4(1), pp. 458-464.

88. Yadav P.J., Jadhav S.S., Mohite S.K. development and validation of rp-hplc method for alogliptin benzoate in bulk drug and dosage form (2014) International Journal of Pharmacy and Pharmaceutical Drug Research, 1(2), PP. 1-9.

89. Mowaka, S., Elkady, E.F., Elmazar, M.M., Ayoub, B.M. Enhanced LC-MS/MS determination of alogliptin and metformin in plasma: Application to a pharmacokinetic study (2017) Micro chemical Journal, 130, pp. 360-365.

90. Bertol, C.D., Friedrich, M.T., Carlos, G., Froehlich, P.E. Analytical stability-indicating methods for alogliptin in tablets by LC-CAD and LC-UV (2017) Journal of AOAC International, 100 (2), pp. 400-405.

91. Kashyap R., Srinivasa U. Development and validation of HPLC method for the simultaneous estimation of pioglitazone and alogliptin in bulk and dosage form (2014) International Journal of Current Research, 6(11), pp.10201- 10207.

92. Ahmed M., Anusha M., Satishkumar S.A., Kuppast I.J, Siddalingaswamy M.S., Ravi M.C. RP-HPLC method development and validation for simultaneous estimation of alogliptin and pioglitazone in combined tablet dosage form (2014) World Journal of Pharmacy and Pharmaceutical Sciences, 4(1), PP. 863-874.

93. Swathi K., Swathi K., Chaitanya M. Method development for the Simultaneous Estimation of Metformin and Alogliptin by using RP-HPLC (2015) International Journal of Pharma Research and Health Sciences, 3(3), pp.747-753.

94. Runja C., Ravikumar P., Avanapu S.R. Stability indicating RP-HPLC method for simultaneous estimation of alogliptin benzoate and metformin hydrochloride in tablet dosage form (2016) International Journal of Pharmacy and Pharmaceutical Sciences, 8(1), pp. 116-120.

95. Mabrouk M.M., Hammad S.F., Mansour F.R., Amer M.M. Development and validation of a reversed phase HPLC method for simultaneous determination of antidiabetic drugs alogliptin benzoate and pioglitazone HCl (2016) Der Pharmacia Sinica, 7(2), pp. 32-40.

96. Surati, J.S., Patel, V.B. Study of degradation behavior of alogliptin benzoate by stability indicating high performance thin layer chromatographic method (2017) Asian Journal of Chemistry, 29 (7), pp. 1607-1611.

97. Bodiwala, K.B., Shah, S., Thakor, J., Marolia, B., Prajapati, P. Degradation kinetics study of alogliptin benzoate in alkaline medium by validated stability-indicating HPTLC method (2016) Journal of AOAC International, 99 (6), pp. 1505-1512.

98. Lu, Y., Yang, D., Li, Z., Hang, T., Song, M. Isolation and characterization of related substances in alogliptin benzoate by LC-QTOF mass spectrometric techniques (2016) Journal of Pharmaceutical and Biomedical Analysis, 128, pp. 253-263.

99. Mayasa, V., Swapna, V., Pati, N.B., Yadav, G., Gupta, V.R.M. Analytical method development and validation of Alogliptin by RP-HPLC method (2016) International Journal of Pharmacy and Technology, 8 (2), pp. 12958-12966.

100. Balaji, N., Sultana, S. Sensitive determination of related substances in pioglitazone hydrochloride by HPLC (2017) International Journal of Applied Pharmaceutics, 9 (2), pp. 34-41.

101. El-Zaher, A.A., Elkady, E.F., Elwy, H.M., Saleh, M.A. Simultaneous determination of metformin, glipizide, repaglinide, and glimepiride or metformin and pioglitazone by a validated lc method: Application in the presence of metformin impurity (1-cyanoguanidine) (2016) Journal of AOAC International, 99 (4), pp. 957-963.

102. Mohamed, A.M.I., Mohamed, F.A.F., Ahmed, S., Mohamed, Y.A.S. An efficient hydrophilic interaction liquid chromatographic method for the simultaneous determination of metformin and pioglitazone using high-purity silica column (2015) Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 997, pp. 16-22.

103. Prasad, P.S., Imam, S.S., Aqil, M., Rizwan, M., Sultana, Y., Ali, A. Validated reversed phase HPLC method for determination of pioglitazone hydrochloride in bulk drug and tablet formulations (2015) Journal of Analytical Chemistry, 70 (6), pp. 744-746.

104. Srinivasulu, D., Sastry, B.S., Prakash, G.O., Archana, D.N.S.S. A new RP-HPLC method for separation and determination of process related impurities in Pioglitazone hydrochloride API (2014) Journal of Scientific and Industrial Research, 73 (9), pp. 618-621.

105. Wang, L.-H., Song, Y.-L. Determination antidiabetic drugs of pioglitazone based on silver electrodeusing in a flow through a voltammetric sensor (2014) Research Journal of Pharmaceutical, Biological and Chemical Sciences, 5 (3), pp. 1160-1169.

106. Elrefay, H., Ismaiel, O.A., Hassan, W.S., Shalaby, A. Development and validation of a stability-indicating HPLC-UV method for the determination of pioglitazone hydrochloride and metformin hydrochloride in bulk drug and combined dosage form (2013) Asian Journal of Pharmaceutical and Clinical Research, 6 (SUPPL.4), pp. 116-120.

107. Kommana, R., Devarapalli, R.S. Development and validation of HPLC and UV spectrophotometric methods for determination of pioglitazone hydrochloride in bulk and its formulations (2013) Der Pharmacia Lettre, 5 (1), pp. 269-278.

108. Mirza, A.Z., Arayne, M.S., Sultana, N. RP-LC method for the simultaneous determination of gliquidone, pioglitazone hydrochloride, and atorvastatin in formulations and human serum (2013) Journal of AOAC International, 96 (1), pp. 56-59.

109. Sachin, J., Hate, M., Vaidya, V., Sudesh, B., Yogesh, S., Rajesh, B. Method development and validation of simultaneous determination of active ingredients i.e. Pioglitazone and glimepride by HPLC from combined tablet formulation (2012) International Journal of Pharmaceutical Sciences, 4 (2), pp. 1958-1964.

110. Ayoub B.M., Abdel-Aziz O. A guide for using experimental design in chromatographic method development: Applied to the analysis of selected anti-diabetic pharmaceutical combinations (2016) Pharmazie, 71 (12), pp. 683-690.

111. El-Bagary R.I., Elkady E.F., Ayoub B.M. Liquid chromatographic methods for the determination of vildagliptin in the presence of its synthetic intermediate and the simultaneous determination of pioglitazone hydrochloride and metformin hydrochloride (2011) International Journal of Biomedical Science, 7 (3), pp. 201-208. Electrophoresis 34 (2013) 862–869.

112. K. Yamashita, H. Murakami, O. Teruaki, et al., High-performanceliquid chromatographic determination of pioglitazone and its meta-bolites in human serum and urine, J. Chromatogr. B Anal. Technol.Biomed. Life Sci. 677 (1996) 141–146.

113. P. Sripalakit, P. Neamhom, A. Saraphanchotiwitthaya, High-performance liquid chromatographic method for the determinationof pioglitazone in human plasma using ultraviolet detection and itsapplication to a pharmacokinetic study, J. Chromatogr. B Anal. Technol. Biomed. Life Sci. 843 (2006) 164–169.

114. Chinnalalaiah, R., Pigili, R., Avanapu, S.R. Liquid chromatography and tandem mass spectrometry method for quantitative determination of pioglitazone and its metabolite 5-hydroxy pioglitazone in human plasma [Méthode de détermination quantitative, rapide et sensible, par chromatographie liquide et spectrométrie de masse en tandem de la pioglitazone et son métabolite, 5-hydroxy pioglitazone, dans le plasma humain] (2017) Annales Pharmaceutiques Francaises, 75 (2), pp. 105-111.

115. E. Tahmasebi, Y. Yamini, A. Saleh, Extraction of trace amounts of pioglitazone as an anti-diabetic drug with hollow fiber liquid phasemicroextraction and determination by high-performance liquidchromatography-ultraviolet detection in biologicalfluids, J. Chroma-togr. B Analt. Technol. Biomed. Life Sci. 877 (2009) 1923–1929.

116. C.H. Ravikanth, A.A. Kumar, V.U. Kiran, et al., Sensitive and rapid HPLC method for the determination of pioglitazone in rat serum, Int.J. Pharm. Sci. Drug Res. 3 (2011) 38–41.

117. K.S. Lakshmi, T. Rajesh, S. Sharma, Determination of pioglitazoneand glimepiride in pharmaceutical formulations and rat plasma byRP-LC, Int. J. Pharm Tech Res. 1 (2009) 496–499.

118. Zhang, X., Peng, Y., Wan, P., Yin, L., Wang, G., Sun, J. Simultaneous determination and pharmacokinetic study of metformin and pioglitazone in dog plasma by LC-MS-MS (2014) Journal of Chromatographic Science, 52 (1), pp. 52-58.

119. Kawaguchi-Suzuki, M., Bril, F., Sanchez, P.P., Cusi, K., Frye, R.F. A validated liquid chromatography tandem mass spectrometry method for simultaneous determination of pioglitazone, hydroxypioglitazone, and ketopioglitazone in human plasma and its application to a clinical study (2014) Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 969, pp. 219-223.

120. Z. Islambulchilar, H. Valizadeh, P. Zakeri-Milani, Rapid HPLCdetermination of pioglitazone in human plasma by proteinPioglitazone: A review of analytical methods 301precipitation and its application to pharmacokinetic studies, J. AOACInt. 93 (2010) 876–881.

121. M.S. Arayne, N. Sultana, A.Z. Mirza, Simultaneous determination of gliquidone, pioglitazone HCl, and verapamil in formulation and human serum by RP-HPLC, J. Chromatogr. Sci. 49 (2011) 114–117.

122. G.R.K. Reddy, V.S.N. Rao, Development and validation of stability indicating assay method for pioglitazone drug substance by reverse phase HPLC, J. Global Trends Pharm. Sci. 3 (2012) 584–596.

123. S. Sharma, M.C. Sharma, S.C. Chaturvedi, Study of stressed degradation behavior of pioglitazone hydrochloride in bulk and pharmaceutical formulation by HPLC assay method, J. Optoelectron. Biomed. Mater. 1 (2010) 17–24.

124. Parthiban, C., Bhagavan Raju, M., Sudhakar, M., Siddartha, B. Simultaneous determination and validation of pioglitazone and glimepiride in tablet dosage form by HPTLC method (2013) International Journal of Pharmacy and Pharmaceutical Sciences, 5 (4), pp. 619-622.

125. Mohamed, A., Mohamed, F., Ahmed, S., Mohamed, Y. New and selective HPTLC-Densitometric method for determination of pioglitazone hydrochloride (2013) Journal of Planar Chromatography - Modern TLC, 26 (3), pp. 209-214.

126. Kumari Karra, V., Rao Pilli, N., Kumar Inamadugu, J., Seshagiri Rao, J.V.L.N. Simultaneous determination of pioglitazone and candesartan in human plasma by LC-MS/MS and its application to a human pharmacokinetic study (2012) Journal of Pharmaceutical Analysis, 2 (3), pp. 167-173.

127. A.M.R.L. Saber, Determination of pioglitazone hydrochloride intablets by high-performance liquid chromatography, Pak. J. Anal. Environ. Chem. 9 (2008) 118–121.

128. A. Jedlicka, J. Klimes, T. Grafnetterova, Reversed-phase HPLCmethods for purity test and assay of pioglitazone hydrochloride in tablets, Pharmazie 59 (2004) 178–182.

129. D.B. Wanjari, N.J. Gaikwad, Stability indicating RP-HPLC method for determination of pioglitazone from tablets, Indian J. Pharm. Sci.67 (2005) 256–258.

130. R.T. Sane, S.N. Menon, S. Inamdar, et al., Simultaneous determination of pioglitazone and glimepiride by high-performance liquid chromatography, Chromatographia 59 (2004) 451–453.

131. J. Swapna, C. Madhu, M. Srivani, et al., Analytical method development and method validation for the simultaneous estimation ofmetformin hydrochloride and pioglitazone hydrochloride in tablet dosage form by RP-HPLC, Asian J. Pharm. Anal. 2 (2012) 85–89.

132. Kale, D., Kakde, R. Simultaneous determination of pioglitazone, metformin, and glimepiride in pharmaceutical preparations using HPTLC method (2011) Journal of Planar Chromatography - Modern TLC, 24 (4), pp. 331-336.

133. V. Sriram, K. Sriram, J. Angirekula, et al., Development and validation of stability indicating reverse phase HPLC method forthe determination of impurities in pioglitazone hydrochloride, Int. J. Pharm. Biomed. Sci. 3 (2012) 89–96.

134. A. Karthik, G. Subramanian, C.M. Rao, et al., Simultaneous determination of pioglitazone and glimepiride in bulk drug and pharmaceutical dosage form by RP-HPLC method, Pak. J. Pharm.Sci. 21 (2008) 421–425.

135. D. Jain, S. Jain, D. Jain, et al., Simultaneous estimation of metforminhydrochloride, pioglitazone HCl, and glimepiride by RP-HPLC in tablet formulation, J. Chromatogr. Sci. 46 (2008) 501–504.

136. Deng, L.-J., Wang, F., Xie, Z.-H., Xiao, Y.-W., Li, H.-D. Simultaneous determination of pioglitazone and its two active metabolites in human plasma by HPLC-MS (2005) Chinese Pharmaceutical Journal, 40 (10), pp. 772-774.

137. Gumieniczek, A., Hopkała, H., Berecka, A. Reversed-phase thin-layer chromatography of three new oral antidiabetics and densitometric determination of pioglitazone (2004) Journal of Liquid Chromatography and Related Technologies, 27 (13), pp. 2057-2070.

138. M. Sarat, P.M. Krishna, C. Rambabu, RP-HPLC method for estima-tion of saxagliptin and pioglitazone in tablets, Int. Res. J. Pharm. 3(2012) 399–402.

139. T.M. Kalyankar, M.R. Badgujar, R.B. Kakde, Simultaneous determi-nation of pioglitazone HCl and glimepiride by RP-HPLC in pharma-ceutical dosage form, J. Pharm. Res. 3 (2010) 3078–3080.

140. F.H. Havaldar, D.L. Vairal, Simultaneous estimation of glimepiride, rosiglitazone and pioglitazone hydrochloride in the pharmaceutical dosage form, J. Chem. 7 (2010) 1326–1333.

141. Xue, Y.-J., Turner, K.C., Meeker, J.B., Pursley, J., Arnold, M., Unger, S. Quantitative determination of pioglitazone in human serum by direct-injection high-performance liquid chromatography mass spectrometry and its application to a bioequivalence study (2003) Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 795 (2), pp. 215-226.

142. M.B. Shankar, V.D. Modi, D.A. Shah, et al., Estimation of pioglitazonehydrochloride and metformin hydrochloride in tablets by derivative spectrophotometry and liquid chromatographic methods, J. AOAC Int.88 (2005) 1167–1172.

143. G. Nirupa, U.M. Tirupathi, RP-HPLC analytical method development and validation for simultaneous estimation of three drugs: glimepride, pioglitazone and metformin and its pharmaceutical dosage forms, J. Chem. 2013 (2013) 1–8.

144. M.S.V. Sakuntala, S.V.U.M. Prasad, S.S. Devi, et al., A RP-HPLC method development and validation for the simultaneous estimationof glimepiride and pioglitazone HCl in tablet dosage forms, J. Chem. Pharma. Res. 4 (2012) 154–159.

145. G. Navaneethan, K. Karunakaran, K.P. Elango, Simultaneous estima-tion of pioglitazone, glimepiride and glimepiride impurities in combination drug product by a validated stability-indicating RP-HPLC method, J. Chil. Chem. Soc. 56 (2011) 815–818.

146. H. Shweta, S. Dhaneshwar, Development and validation of a HPLC method for the determination of metformin HCl, gliclazide and piogliglitazone hydrochloride in multicomponent formulation, Webmed Central Pharm. Sci. 1 (2010) 1–16.

147. V. Kumar, M. Sudhakar, Y. Padmanabha Reddy, et al., Method development and validation for simultaneous estimation of pioglita-zone and glimepiride in tablet dosage form by RP-HPLC and UV-spectrophotometric method, Curr. Pharm. Res. 2 (2011) 404–410.

148. D.C. PremAnand, K.L. Senthilkumar, B. Senthilkumar, et al., A new RP-HPLC method development and validation for simultaneous estimation of telmisartan and pioglitazone in pharmaceutical dosage form, Int. J. Chem Tech Res. 3 (2009) 448–454.

149. K.S. Lakshmi, T. Rajesh, S. Sharma, et al., Development and validation of liquid chromatographic and UV derivative spectro-photometric methods for the determination of metformin, pioglitazoneand glimepiride in pharmaceutical formulations, Der. Pharm. Chem. 1(2009) 238–246.

150. M.C. Sharma, S. Sharma, D.V. Kohli, et al., Micellar liquid chromatographic analytical method development and validation of determination of atorvastatin calcium and pioglitazone in tablet dosage form, Der. Pharm. Chem. 2 (2010) 273–280.

151. N. Rashmithaa, S.G. Hiriyanna, C.H.S. Rao, A validated stability indicating HPLC method for the determination of impurities inpioglitazone hydrochloride, Der. Pharm. Chem. 2 (2010) 426–433.

152. A. Madhukar, K. Naresh, C.N. Kumar, et al., Rapid and sensitive RP-HPLC analytical method development and validation of pioglitazonehydrochloride, Der. Pharm. Chem. 3 (2011) 128–132.

Received on 19.08.2017 Modified on 25.08.2017

Research J. Pharm. and Tech. 2017; 10(9): 3161-3172.

DOI: 10.5958/0974-360X.2017.00563.7