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° Li et al., (2003)  reported a developed HPLC method for the determination of Diltiazem concentration in human plasma and its application to pharmacokinetics. Diltiazem and Diazepa (ISTD) were extracted from the plasma with mixed organic solution i.e., hexane, chloroform and isopropanol (60:40:5 v/v/v) by using Spherisorb C18 column at a flow rate of 1.2 mL/min, then it was detected by Ultraviolet absorbance at 239nm. The Linearity range was 0-300 mg/mL and LOD was 3 mg/mL. The % RSD was 3.5-6.8 % for within-day analysis and 6.2-8.4 % for between day analyses. The peak plasma levels were obtained approximately in the range of 118.5 ± 14.3 ng/mL at 3.1 ± 0.4 hours. The AUC was 793.1 ± 83.1 ng.h/mL.
° Nisar-ur-Rahman et al., (2005)  reported a developed and Validated method for the analysis of Diltiazem in human plasma by using improved HPLC. Diltiazem and verapamil (ISTD) were extracted from the plasma with a mixture of hexane and diethyl ether. [0.1M ammonium dihydrogen phosphate: ACN (62:38v/v)] used as a mobile phase. By using Lichrospher 100 RP18 (5mm, 250-x 4.6mm ID) column at flow rate of 1.0ml/min and Ultraviolet absorbance of samples were detected at 238 nm. Linearity range was 5-160 mg/mL and LOD was 2.5mg/mL. The % mean recovery was 90 %.
° Zendelovska et al., (2003)  reported a developed HPLC method based on solid phase and liquid-liquid extraction for determination of Diltiazem concentration in human plasma. A 5 microm lichrocart Lichrospher 60 RP-select B column was used for the drug estimation by using a mobile phase Acetonitrile: potassium dihydrogen phosphate (pH 5.5), 0.025 mol-1 35:65(v/v) and its flow rate was 15 mL/min-1. The detection wave length was at 215 nm and linearity range 20.0-500.0mg/mL-1.
° Rustum et al., (1989) reported a rapid, selective, reversed-phase column HPLC method for the determination of the Diltiazem in human whole blood and plasma by using salting out extraction procedure. In this method the drug was extracted by using solvent extraction procedure, after that the by using ammonium sulphate organic solvents get salting-out. Reversed- phased column 15 cm-4.1 mm, with isocratic elution by using a mobile phase of ACN: 0.01 M tetra butyl ammonium hydroxide (60:40 v/v).And the separation was completed less than 15 min. LOD was10 ng/mL. At 50 µ injection volume the signal to noise was 3.
° Varghese et al., (1982) reported a rapid, selective and reproducible HPLC method for the analysis of Diltiazem and its metabolite (Desacetyl Diltiazem) in plasma. By using MTBE (methyl tert-butyl ether) extraction solvent the analyte and internal standard (verapamil) were extracted, then back extracted in to sulphuric acid. Finally the extracted sample analysed chromatographically with UV detection over the concentration range of 10-1000 ng/mL. And its average coefficient of variation was 5.4 % and 8.3 % for Diltiazem and Desacetyl Diltiazem respectively.
° Dube et al., (1988) reported a rapid, reproducible HPLC method for the determination of diltiazem and its metabolites in human plasma. In this method the plasma samples were extracted with MTBE, and it was extracted into 0.017 M phosphoric acid. The separation was done by using 3µ, 15 cm ODS column with UV detection at 237 nm. The overall % was found to be more than 85 %. Linearity range was10-250 ng/ml and its inter-day and intera-day coefficients were observed less than 12 %.
° Ascalone et al., (1994)  reported a developed HPLC -solid phase extraction method to overcome instability and interfering problems during Quantitation of Diltiazem and its main metabolites in human. SPE procedure used for extracting drug and its metabolites on ASPEC-Gilson device combined with HPLC. 0.5 ml of 0.1 M Ammonium dihydrogen phosphate: ACN mixture (20:80 v/v) having 0.06 % triethyl amine used as extraction solvent. C18 silica column was used, UV absorbance was 238 nm. LOQ was 2.5 and 2 ng/mL-1. The linearity range was 10-200 and 5-100 ng/ml-1for Diltiazem and its Metabolites in human plasma.
° Goebel et al., (1985)  reported a method to determine Diltiazem and its four metabolites by using HPLC and applications to Pharmacokinetic studies. Diltiazem and propionyl Desacetyl Diltiazem (ISTD) were extracted from the plasma with MTBE followed by back- extraction in to 0.01M HCl. Chromatographic estimation done by using methanol-Ammonium bromide-ACN mobile phase, C18 column and Ultraviolet absorbance at 237nm. Linearity ranges 1-800 ng/mL and LOD 0.1-0.2ng/mL.
° Rutledge et al., (1993)  reported a developed method by using silanol deactivated short alkyl chain column for the determination of Diltiazem and its metabolites using HPLC. Alkalinized plasma was extracted by n-hexane-isopropanol mixture (95.5 v/v) fallowed by back-extraction in to 5 mM sulphuric acid. Imipramine used as the internal standard for the analysis. The ultraviolet Detection was at 237 nm. The concentration range was 20-400 nm LOD was 4, 2 and 4 ng/mL for Diltiazem and its metabolites (Desacetyl and Desmethyl Diltiazem).Within day and between days coefficient of variations was found to be less than 10 %.
° Hogland et al., (1987)  reported a HPLC method by the addition of amine to mobile phase during solid phase extraction. Trans isomer as internal standard for the determination of Diltiazem and its metabolites. Plasma samples are saturated with sodium chloride and made alkaline before sample extraction. Triethyl amine is also added. Ultraviolet detection was at 237nm.
° Hubert et al., (1991)  reported an optimised, validated HPLC method using liquid-solid phase extraction procedure to determine diitiazem and des acetyl diitiazem concentrations in human plasma. By using disposable extraction cartridges the analytes and metabolites isolated. The isolated analyte/metabolites get separated on highly deactivated octyl silica column with a mobile phase [Methanol: 0.05M phosphate buffer (pH 7.4) (62:38 v/v)]. 0.1 ml of internal standard was added to the plasma samples at first before extraction of samples. DECs cartridges were condition done by using methanol and phosphate buffer (pH 7.4). Analyte using 0.16 ml of methanol the analyte/metabolites were eluted.0.14 ml of buffer solution was passed through the cartridges and finally 0.25 ml of final extract was injected to the HPLC column. The Analyte /Metabolite were monitored photo metrically at 238 nm and the LOD was 0.8ng/mL.
° Georgita et al., (2008)  reported a Liquid chromatographic and ESI/MS2 Non linear calibration method for determination of diitiazem and its two metabolites in human plasma samples and applications to bioequivalence studies. Sample preparation was done by using protein precipitation extraction method with ACN. Sample concentrations determined by using reversed-phase mechanism with isocratic elution. A good separation of analyte and Metabolites obtained with in 15 min. During the validation studies non linear calibration were observed. The lower LOQ range was 0.6-1ng/mL. This method was applied to bioequivalence study of Single dose (120 mg) solid oral dose (tablets).
° Dasanidi et al., (2009)  reported a high through output, robust and validated method for simultaneous determination of Diltiazem and its Metabolites in human plasma LC-MS/MS method with electro spray ionization (ESI) and applications to bioequivalence studies. By using (UPLC-MS/MS) analytes were chromatographed on ACQUITY UPLC BHE C (18) column with 100 mm x 2.1 mm and i.d., 1.7 microm) with an isocratic elution at a flow rate of 0.2 mL/min by using 10 mM ammonium acetate as mobile buffer-ACN (25:75 v/v), Ziprasidone is used as a internal standard for the Quantitation of the analyte and its metabolites. The LOQ was 0.48 and 0.24 for Analyte and its metabolites. The % recovery was 77.4 %, 76.0 %, 77.5 % and 74.1 % for Analyte, Metabolites and ISTD.