ABSTRACT
A specific GC-MS method has been developed, optimized and validated for the determination of five genotoxic impurities namely Methyl bromide (Me.-Br), Ethyl bromide (Et.-Br), Isopropyl bromide (Ipr.-Br), n-Propyl bromide (n-Pr.-Br) and n-Butyl bromide (n-But.-Br) in Divalproex sodium (DPS) drug substance. Chromatographic separation of five genotoxic impurities was achieved on DB-1 column (30 m × 0.32 mm, 3.0 µm), consists of 100% dimethyl polysiloxane as stationary phase and passing helium carrier gas. The mass fragments (m/z) were selected for the quantification of Me.-Br (m/z 94), Et.-Br (m/z 108), Ipr.-Br (m/z 122), n-Pr.-Br (m/z 122) and n-But.-Br (m/z 136). Bromide ion (m/z 79) was the qualifier ion for the analytes [(Me.-Br), (Et.-Br), (Ipr.-Br), (n-Pr.-Br) and (n-But.-Br)]. The performance of the method was assessed by evaluating the specificity, linearity, sensitivity, precision and accuracy experiments. The established limit of detection and limit of quantification values for the genotoxic impurities were in the range of 0.005-0.019 µg mL-1. The correlation coefficient values of the linearity experiment were in the range of 0.9947-0.9983. The average recoveries for the accuracy were in the range of 97.6-111.3%. The results proved that the method is suitable for the determination of Me.-Br, Et.-Br, Ipr.-Br, n-Pr.-Br and n-But.-Br contents in divalproex sodium.
Subject(s)
Drug Contamination , Gas Chromatography-Mass Spectrometry/methods , Mutagens/analysis , Valproic Acid/analysis , Limit of Detection , Linear Models , Reproducibility of Results , Valproic Acid/chemistry , Valproic Acid/standardsABSTRACT
A specific GC method has been developed, optimized and validated for the determination of seven related substances namely N,N-dimethyl valpronamide, valeric acid, 2-methyl valeric acid, 2-ethyl valeric acid, 2-isopropyl valeric acid, 2-n-butyl valeric acid and 2-propyl-2-pentenoic acid in divalproex sodium (DPS) drug substance. Chromatographic separations of these seven impurities were achieved on DB-FFAP column (30 m × 0.53 mm, 1.0 µm), which consists nitroterephthalic acid modified polyethylene glycol material as stationary phase. DPS is a coordination complex of the sodium valproate and valproic acid (VPA). Nonanoic acid is used as internal standard. All the seven related substances, VPA and nonanoic acid were extracted into dichloromethane and monitored by GC with flame ionization detector. The performance of the developed method was assessed by evaluating specificity, linearity, sensitivity, precision, accuracy and robustness. Forced degradation experiments were conducted to evaluate the degradation behavior of DPS. The established limits of detection (LODs) and limits of quantification (LOQs) values for the related substances were in the ranges of 4-5 and 12-15 µg mL-1, respectively. Further, for VPA, LOD and LOQ values were 4 and 12 µg mL-1, respectively. The correction factors of these related substances with respect to VPA and lie between 0.92 and 1.44. The average recoveries were in the range of 92.4-108.4%.
Subject(s)
Chromatography, Gas/methods , Valproic Acid , Limit of Detection , Linear Models , Pentanoic Acids/analysis , Pentanoic Acids/chemistry , Reproducibility of Results , Valproic Acid/analogs & derivatives , Valproic Acid/analysis , Valproic Acid/chemistryABSTRACT
A simple and sensitive ion chromatography method has been developed for the simultaneous assay of ibandronate sodium drug substance and the determination of its impurities. The separation was achieved on Allsep™ anion column 150 mm × 4.6 mm, 7 µm particle diameter. The mobile phase consisted of 1% (v/v) aqueous formic acid and acetone 98:2% (v/v); flow rate 1.0 ml min(-1) at ambient temperature. The analytes were monitored by conductometric detector. The drug substance was subjected to stress conditions of hydrolysis, oxidation, photolytic, thermal and humidity degradation. Considerable degradation was achieved only under oxidative conditions. Mass balance was demonstrated in all stress conditions. The method was validated for specificity, precision, linearity, solution stability and accuracy. The limits of detection (LOD) and limits of quantification (LOQ) for impurities were in the range of 0.36-0.80 µg ml(-1) and 1.00-2.40 µg ml(-1), respectively. For ibandronate LOD was 38 µg ml(-1) and LOQ was 113 µg ml(-1). The average recoveries for impurities and ibandronate were in the range of 99.0-103.1% and the method can be successfully applied for the routine analysis of ibandronate sodium drug substance.
Subject(s)
Diphosphonates/analysis , Drug Contamination , Chromatography, Ion Exchange , Chromatography, Reverse-Phase , Diphosphonates/chemistry , Diphosphonates/pharmacology , Drug Stability , Humans , Humidity , Hydrolysis , Ibandronic Acid , Photolysis , Reproducibility of Results , Sensitivity and Specificity , TemperatureABSTRACT
102 cases of idiopathic adolescent scoliosis seen over a period of 5 years were studied. 59 patients who were treated surgically and followed up for a minimum of 48 months, fell into one of two groups: Group I - those operated on within 3 years following the adolescent growth spurt, and Group II - those who were operated on at or after skeletal maturity. 35 patients were treated by Harrington instrumentation and posterior fusion and 24 by Harrington instrumentation, segmental sublaminar wiring and posterior fusion. In 7 patients anterior release was performed initially. In Group I, the extent of deformity correction and elimination of the rib hump were better, and complications such as neurological deficit, hook dislodgement and implant breakage were encountered less frequently. Harrington instrumentation, segmental sublaminar wiring and posterior fusion gave better results than instrumentation and fusion. Our results suggest that surgical correction should be done within 3 years following growth spurt, i.e. 14 to 16 years of age.