ABSTRACT
OBJECTIVE：To es tablish a method for the content determination of heavy metals [lead （Pb），cadmium（Cd）， copper （Cu）， mercury （Hg）] and harmful elements [arsenic （As）] in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules. METHODS ：The samples were conducted pretreatment by microwave digestion instrument and determined by inductively coupled plasma mass spectrometry （ICP-MS）using elements germanium ，indium，bismuth as internal standard. RESULTS ：The linear ranges of Pb ，As，Cu，Cd and Hg were 1-20，0.5-10，5-100，0.5-10 and 0.2-4 ng/mL， respectively （all r＞0.997）. The limits of detection （LODs） were 0.041 1，0.013 2，0.057 3，0.009 0，0.005 4 ng/mL， respectively. The limits of quantification （LOQs）were 0.137 0，0.044 0，0.191 0，0.030 0，0.018 0 ng/mL，respectively. RSDs of precision and repeatability tests were all less than 6％. RSDs of stability tests （28 h）of Pb ，As，Cu and Cd were all less than 5％， and that of stability test （28 h）of Hg was less than 7％. The average recoveries were 89.44％（RSD＝5.87％，n＝9），99.56％ （RSD＝5.46％ ，n＝9），96.12％（RSD＝4.62％ ，n＝9），105.82％（RSD＝2.80％ ，n＝9）and 90.23％（RSD＝3.59％ ，n＝9）， respectively. Five elements were all detected in 63 batches of samples ，and the contents of them were 0.191 0-1.527 6，0.002 5- 0.047 4，0.034 1-1.549 0，0.001 5-0.078 8 and 0.001 9-0.005 4 mg/kg，respectively. CONCLUSIONS ：The method is simple ， sensitive and accurate. It is suitable for simultaneous determination of 5 elements in Pediatric paracetamol artificial cow-bezoar and chlorphenamine maleate granules.
ABSTRACT
OBJECTIVE：To evaluate the dissolution behavior consistency between the generic drugs and original drugs of Oxcarbazepine scored tablets ，and to compare the appearance ，the friability of the split portions ，loss of mass of the split portions as well as crystal form and morphology of raw material from different enterprises. METHODS ：HPLC method was adopted. The paddle method （rotation speed of 60 r/min，the temperature of 37.0℃）was adopted to determine accumulative dissolution rate of generic and original drugs in 4 mediums [ 0.6％ SDS hydrochloric acid solution （pH＝1.2），0.6％ SDS acetate buffer solution （pH＝4.5），0.6％ SDS phosphate buffer solution （pH＝6.8）and 0.6％ SDS water solution]. The similarity factor method was used to evaluate the similarity of dissolution curves as well as intra-batch uniformity of the split portions and whole tablets. The friability tester and electronic balance were used to determine the friability and the loss of mass of the split portions. X-ray diffractometer and scanning electron microscope were used to observe the crystal form and crystal morpho logy of the raw materials of different enterprises. RESULTS ：The linear range of oxcarbazepine was LOD was 0.04 μg/mL；RSDs of precision ，stability，reprodu- cibility and durability tests were lower than 2.0％；the reco- veries were 99.80％-101.63％（RSD＝0.37％-0.91％，n＝3）. The average cumulati ve dissolution rate of generic drug A ， generic drug B and original drug in 4 different dissolution media at 90 min were 92％，87％，90％ [0.6％ SDS hydrochloric acid solution（pH＝1.2）]；94％，94％，90％ [0.6％ SDS acetate buffer solution （pH＝4.5）]；95％，95％，91％ [0.6％ SDS phosphate buffer solution （pH 6.8）]；97％，98％，95％（0.6％ SDS water solution ）. The similarity factors of generic drug A ，generic drug B and original drug in 4 kinds of different dissolution media were 66 and 81，71 and 69，71 and 61，59 and 39. In the first 15 min，the difference of dissolution rate of split portions and whole tablets were －3％-13％，－2％-24％ and －3％-7％ for generic drug A ， generic drug B and original drug ，respectively. RSDs of accumulative dissolution rate of split portions and whole tablets were 6％-14％ and 2％-9％ for generic drug A （n＝12），4％-10％ and 1％-8％ for generic drug B （n＝12）and 2％-7％ and 2％-8％ for original drug. The appearance of the original drug was fusiform ，and the notch was deep ；the shape of the generic drug was different from each other ，and the notch of the generic drug was significantly shallower than that of original drug. The friability ， the loss of mass of the split portions for generic drug A and generic drug B ，original drug were 0.62％and 0.67％，0.12％ and 0.11％，0.08％ and 0.05％. The domestic raw materials possessed irregular lumps and debris ，while the raw materials produced by original drug enterprises possessed regular flat cuboids and regular strips with little debris ；but X-ray diffraction peaks of them were basically the same. CONCLUSIONS ：The dissolution behavior of generic drug A in 4 medium is consistent with that of the original drug；dissolution behavior of generic drug B in water containing 0.6％SDS is different from that of the original drug ；there is no significant change in the homogeneity of the original drug before and after splitting ，but the homogeneity of the generic drug A and B after splitting is lower than that of the whole tablet ；the fragility of generic drugs and loss of mass of split portions are higher than those of the original drugs ；two kinds of raw material have the same crystal form but different crystal morphology.