Research On The Detection Of Synthetic Pharmaceuticals As Adulterants In Chinese Patent Medicine And Health Care Products Used For Anti-obesity And Anti-diabetes

ObjectiveSome synthetic pharmaceuticals are illegally adulterated in health products such as Chinese patent medicine(CPM)and health care products(HCP).These products may result in serious adverse health events.The traditional detection methods usually require expensive equipments and experienced personnel.They donot suitable for basic stuffs to use,with weak timeliness.MS is the main confirmation method for detecting the illegal adulteration of synthetic pharmaceuticals.But the standard substances are usually expensive.The cost is very high for users buying standard substances to establish MS database.So it has low cost performance and restricts the detection ability.For the past few years,structure modificatory analogues were illegally added in CPM and HCP,with the purpose of evading routine legal inspection.They brought great challenges to supervision and detection.Therefor,This work established a simple method for detecting thiazolidinediones in CPM and HCP used for anti-diabetes with less environmental pollution and srtong timeliness.This work also improved and perfected the method validation metrics of sibutramine rapid screening method.Meanwhile,the MS database was established,which contained characteristic fragments of certain components.It can be used to detect known illegal adulteration of synthetic pharmaceuticals without standards,as well as analogues.MethodsThis work investigated the temperature influence on precipitation reaction and liquid-liquid extraction(LLE)rate of sibutramine rapid screening method.According to the molecular structure characteristic and physical-chemical properties of thiazolidinediones,the rapid screening method was established.This work also investigated some metrics that influence performance.The MS database was established by a triple quadrupole mass spectrometer and a quadrupole-time of flight mass spectrometer,according to the 21 synthetic pharmaceuticals in legal methods for detecting illegal adulteration in CPM and HCP used for anti-obesity and anti-diabetes.The collision energy was set at 15,30 and 45 eV,respectively,to obtain rich fragment information.The characteristic fragments of certain components were organized to discover analogues.ResultsThe temperature had little influence on LLE rate of sibutramine in 10 to 25 degrees Centigrade.It mainly affected the precipitation reaction rate.Sibutramine rapid screening method was usable in 15 to 30 degrees Centigrade.The rapid screening method of thiazolidinediones was operated as follows.A test tube method was built.First,a mixed organic solvent(ethanol:ethyl acetate = 2:98,v/v)was applied to extract thiazolidinediones from samples.Second,a LLE was performed with a mixed inorganic acid(phosphoric acid:0.1 mol/L hydrochloric acid = 3:97,v/v)to eliminate interference.In the end,ammonium reineckate was used as detection reagent to detect thiazolidinediones.The transfer efficiencies of rosiglitazone hydrochloride and pioglitazone hydrochloride were both above 39%.The LODs were 0.11 mg and 0.14 mg per aliquot(25 degrees Centigrade),respectively.It had good selectivity.The accuracy was 98%,the sensitivity was 100%,and the specificity was 96.43%.The temperature mainly affected the solubility of the precipitate.It was the main influence factor on LOD.The results detected by two mass spectrometers showed that the fragments had a little differences in different mass spectrometers.The main fragments were both clear.The MS database was established with these same main fragments.This study neatened the characteristic fragments of sibutramine class and biguanides.On the basis of the characteristic fragments,this work discovered a sibutramine analogue during MS screening of health products used for weight loss.The probable structure of this analogue was deduced.ConclusionThis study describes a specific,simple and rapid screening method for thiazolidinediones,with high selectivity,accuracy,sensitivity,and specificity.The detection time of the method for each sample was less than 3 minutes.The rapid screening method can determine whether thiazolidinediones were illegally added to CPM and HCP used for anti-diabetes.This work innovatively made use of mixed solvent to extract target composition,which can overcome the deficiency of single solvent.It could provide certain reference to develop this kind of method.The mass databases can be used for daily MS detection by related researchers and other institutes for food and drug control which have different experiment conditions.In addition to rapid screen known synthetic pharmaceuticals,more importantly,it can identify the analogues.It can expand the detection range of rapid screening,and crack down on illegal adulteration of analogues.