[Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function].

OBJECTIVE: To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function. METHODS: A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated. RESULTS: After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05). CONCLUSION: Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.

A Metabolomics-Based Study on the Discriminative Classification Models and Toxicological Mechanism of Estazolam Fatal Intoxication.

Fatal intoxication with sedative-hypnotic drugs is increasing yearly. However, the plasma drug concentration data for fatal intoxication involving these substances are not systematic and even overlap with the intoxication group. Therefore, developing a more precise and trustworthy approach to determining the cause of death is necessary. This study analyzed mice plasma and brainstem samples using the liquid chromatography-high resolution tandem mass spectrometry (LC-HR MS/MS)-based metabolomics method to create discriminative classification models for estazolam fatal intoxication (EFI). The most perturbed metabolic pathway between the EFI and EIND (estazolam intoxication non-death) was examined, Both EIND and EFI groups were administered 500 mg of estazolam per 100 g of body weight. Mice that did not die beyond 8 hours were treated with cervical dislocation and were classified into the EIND groups; the lysine degradation pathway was verified by qPCR (Quantitative Polymerase Chain Reaction), metabolite quantitative and TEM (transmission electron microscopy) analysis. Non-targeted metabolomics analysis with EFI were the experimental group and four hypoxia-related non-drug-related deaths (NDRDs) were the control group. Mass spectrometry data were analyzed with Compound Discoverer (CD) 3.1 software and multivariate statistical analyses were performed using the online software MetaboAnalyst 5.0. After a series of analyses, the results showed the discriminative classification model in plasma was composed of three endogenous metabolites: phenylacetylglycine, creatine and indole-3-lactic acid, and in the brainstem was composed of palmitic acid, creatine, and indole-3-lactic acid. The specificity validation results showed that both classification models distinguished between the other four sedatives-hypnotics, with an area under ROC curve (AUC) of 0.991, and the classification models had an extremely high specificity. When comparing different doses of estazolam, the AUC value of each group was larger than 0.80, and the sensitivity was also high. Moreover, the stability results showed that the AUC value was equal to or very close to 1 in plasma samples stored at 4 °C for 0, 1, 5, 10 and 15 days; the predictive power of the classification model was stable within 15 days. The results of lysine degradation pathway validation revealed that the EFI group had the highest lysine and saccharopine concentrations (mean (ng/mg) = 1.089 and 1.2526, respectively) when compared to the EIND and control group, while the relative expression of SDH (saccharopine dehydrogenase) showed significantly lower in the EFI group (mean = 1.206). Both of these results were statistically significant. Furthermore, TEM analysis showed that the EFI group had the more severely damaged mitochondria. This work gives fresh insights into the toxicological processes of estazolam and a new method for identifying EFI-related causes of mortality.

Clinical effect of acupuncture based on syndrome differentiation in the treatment of chronic insomnia and its influence on cognitive function / 中国针灸

OBJECTIVE@#To compare the effect of acupuncture based on syndrome differentiation and estazolam in the treatment of chronic insomnia and its influence on cognitive function.@*METHODS@#A total of 90 patients with chronic insomnia were randomly divided into an acupuncture group and a medication group, 45 cases in each group. The acupuncture group was treated with acupuncture at Sishencong (EX-HN 1) and bilateral Shenmen (HT 7), Sanyinjiao (SP 6) combined with compatibility of acupoints based on syndrome differentiation, once a day for 6 d and then rest for 1 d, for a total of 4 weeks. The medication group was treated with oral estazolam tablets before bedtime, 1 tablet each time, for a total of 4 weeks. Before and after treatment, the scores of Pittsburgh sleep quality index (PSQI), mini-mental state examination (MMSE), Montreal cognitive assessment (MoCA) and auditory verbal memory test (AVMT) of the two groups were compared, and the effects were evaluated.@*RESULTS@#After treatment, the PSQI sub-item scores and total scores of the two groups were lower than those before treatment ( P<0.05 ), and above scores in the acupuncture group were lower than those in the medication group ( P<0.05 ); the scores of MMSE, MoCA and AVMT in the two groups were higher than those before treatment ( P<0.05 ), and the scores in the acupuncture group were higher than those in the medication group ( P<0.05 ). The total effective rate of the acupuncture group was 80.0% (36/45), which was higher than 53.3% (24/45) in the medication group (P<0.05).@*CONCLUSION@#Syndrome differentiation acupuncture can improve the sleep quality and cognitive function of patients with chronic insomnia, and the curative effect is better than that of estazolam.

Time course of estazolam in single-strand hair based on micro-segmental analysis after controlled oral administration.

The mechanism of estazolam incorporation into hair was investigated by studying the time course of estazolam along single-strand hair after two oral administration of estazolam at 28 days interval. Estazolam in single hair segments 0.4 mm in length was verified and quantified by ultra-high-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS). The distributions of estazolam within a strand of hair (collected at 12 h, 28 days, and 56 days post-administration) were visualized by micro-segmental analysis. The highest estazolam concentration (1.5-9.9 pg/mm) was detected in the hair bulb region (S1), and it then decreased through the hair shaft to the distal end, with a small fluctuation (0.3-3 pg/mm) near the junction of the hair roots and shafts (S4-S7) 12 h after drug intake. These findings suggested that the incorporation of estazolam occurred in two regions, mainly in the hair bulb and to a lesser extent in the upper dermis zone. Models using internal temporal markers (TIMs) and temporal intervals (TIs) were constructed to estimate the day of estazolam ingestion. The estimation accuracy was within an average error of 1.7 mm and 3.0 mm between the calculated and actual positions, based on the TIMs and TIs 56 days after estazolam intake. These findings can help in further elucidation of the drug incorporation mechanism, which is crucial for interpreting hair analysis results used to reveal individual drug-use history.

Formation and occurrence of disinfection byproducts of benzodiazepine drug estazolam in drinking water of Beijing.

Estazolam (EZ) is a long-acting benzodiazepine (BZD) drug with high clinical consumption in China to treat anxiety, depression and other syndromes. Recently, it has been found as a leading potentially inappropriate medication among hospitalized elderly patients, increasing the risk of falls. It is discharged into the aquatic environment after use and has been frequently detected, ultimately affecting the safety of drinking water. In the present study, the reaction of EZ during chlorination disinfection was investigated in detail with regard to its transformation and kinetics. By means of ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS), four main disinfection byproducts (DBPs) were tentatively identified, and the transformation pathways were speculated to be cleavage at the imine linkage and oxidation on the diazepinone ring. The chlorination reaction rate in the pseudo-first-order kinetic model was significantly affected by free available chlorine (FAC) and pH. The increase in pH value led to a decrease in the reaction rate, while a higher dosage of chlorine resulted in a faster kinetic rate. We further estimated the potential toxicities of EZ and its DBPs using quantitative structure-activity relationship (QSAR) software tools. DBPs exhibited much higher toxicity than EZ and exhibited developmental toxicity and mutagenicity. Finally, a total of 108 drinking water samples were collected in the wet and dry seasons to determine actual residue changes in real environmental conditions. The detection frequency was 29% for EZ, and the highest concentration of 0.60 ng L-1 was found for its DBPs in tap water. No seasonal variations in concentration were observed. Overall, the results indicate that EZ and its DBPs may persist in drinking water, posing potential risks to public health.

"Q-markers targeted screening" strategy for comprehensive qualitative and quantitative analysis in fingerprints of Angelica dahurica with chemometric methods.

Angelica dahurica is a famous functional food and herb. To guarantee quality of A. dahurica, a strategy "Q-markers targeted screening" was successfully developed by sufficient extraction of compounds and the targeted screening of qualitative and quantitative markers calculated through chemometric methods based fingerprints. Accelerated solvent extraction was selected due to its prominent advantages exhibiting the maximum extraction yields and varieties of compounds and especially excellent reproducibility (RSD < 1). After extraction, the fingerprints of A. dahuricae samples were established. For the preliminary herb authenticity, the targeted screening of 23 quantitative markers were performed by similarity analysis and hierarchical cluster analysis based on the fingerprints, which were identified by liquid chromatography tandem mass spectrometry (LC-MS). Subsequently, for further quality control, the targeted screening of nine quantitative markers were done by similarity analysis & linear discriminant analysis, which were determined by LC. Lastly, the strategy was successfully applied to quality assessment of A. dahurica samples.

Clinical efficacy of internet-based cognitive behavioral therapy combined with estazolam for patients with chronic insomnia / 中华行为医学与脑科学杂志

Objective:To investigate the efficacy and safety of internet-based cognitive behavioral therapy for insomnia(iCBT-I) combined with estazolam for patients with chronic insomnia.Methods:Patients with chronic insomnia were randomly assigned to treatment group which were intervened with iCBFI combined with estazolam( n=46) and control group which were intervened with estazolam ( n=43) for 8 weeks according to random number table.Pittsburgh sleep quality index (PSQI) and state-trait anxiety inventory (STAI) were used to measure the anxious state, anxious trait and sleep quality at three time points: before intervention(T1), after one month(T2) and two months(T3). Treatment emergent symptom scale (TESS), blood routine, urine routine, liver and renal function and electrocardiogram were used to measure the safety.The dosage of estazolam was compared between the two groups after two months.χ 2 test and repeated measurement analysis of variance were performed by SPSS 19.0. Results:The PSQI scores of control group and treatment group were (10.41±2.48) vs (9.98±2.96) at T2 and (9.97±2.13) vs (7.82±1.57) at T3.The state anxiety scores of control group and treatment group were (57.27±2.74) vs (56.27±2.89) at T2 and (45.67±2.62) vs (42.67±2.97) at T3.The data of T2 and T3 were statistically significant compared with those before intervention(all P<0.05). Compared with the control group, the treatment group was better on treatment efficiency(86.96% vs 69.77%) at T3( P<0.05). PSQI score, subjective sleep quality, sleep efficiency, sleep disorders, sleep drugs, daytime dysfunction, drug maintenance and adverse reaction were significantly different between the two groups at T3 ( P<0.05). Conclusions:Internet-based cognitive behavioral therapy combined estazolam for insomnia can improve sleep quality, anxious state and trait for chronic insomnia patients.Good safety was improved, as well as reducing the need of drug.So it's worthy of clinic application.

Retention Time and Ion Abundance Ratio of 8 Common Drugs （Poisons） by LC-MS/MS Qualitative Analysis.

ABSTRACT: Objective To investigate the maximum allowable deviations of retention time and ion abundance ratio of the 8 common drugs （poisons） from 3 categories, poisons （methamphetamine, morphine, ketamine）, benzodiazepines （estazolam, midazolam, diazepam, clonazepam） and barbiturates （phenobarbital） in blood, by liquid chromatography-tandem mass spectrometry （LC-MS/MS） in forensic toxicology analysis. Methods The deviations of retention time and ion abundance ratio at 7 low mass concentrations, limit of detection （LOD）, 2LOD, limit of quantitation （LOQ）, 1.5LOQ, 2LOQ, 4LOQ and 6LOQ, were tested by LC-MS/MS after liquid-liquid extraction under the conditions of two chromatographic columns and three chromatographs. Results The deviation of absolute retention time of 98.11% of 8 drugs （poisons） in the blood samples was within the range of ±0.05 min, and that of the relative retention time of 96.21% was within the range of ±0.4%. The maximum deviation of the ion abundance ratio was highly correlated with the mass concentration. When the mass concentration of drugs （poisons） was LOQ or above, more than 95% of the absolute deviation and relative deviation of the ion abundance ratio were in the range of ±25% and ±40%, respectively; when the mass concentration was below LOQ, the range could be expanded to ±35% and ±50%, respectively. Conclusion It is recommended for the determination range of the absolute retention time deviation of 8 common drugs （poisons） to be ±0.1 min and that of the relative retention time deviation to be ±1.0%. The determination range of absolute deviation of the ion abundance ratio should be ±25% when the mass concentration is LOQ or above, and the relative deviation should be ±40%. When the mass concentration is below LOQ, the deviation determination range can be expanded to ±35% and ±50%, respectively.

Detailed quantum mechanical studies on bioactive benzodiazepine derivatives and their adsorption over graphene sheets.

Estazolam (Z1) and related derivatives, adinazolam (Z2), alprazolam (Z3), 4-hydroxyalprazolam (Z4) and triazolam (Z5) have been studied by using various computational tools to analyze their geometry and spectral characteristics. The compounds were found to interact with graphene monolayer results shows that there is enhancement in various physico-chemical descriptors and surface enhanced Raman spectra (SERS). The various reactive descriptors obtained from the FMO analysis predict the reactive nature of the compound. The various lone pair/sigma to pi conjugation was analyzed using NBO formalism, which provides valuable information about intra molecular electron transfer which is vital in predicting the inherent stability of the molecule. Simulated electronic spectra using TD-DFT and CAM-B3LYP functional are discussed in detail with respect to electronic transitions and light harvesting efficiency. Suitability of candidates as a photo sensitizer in dye sensitized solar cells was studied and 4-Hydroxyalprazolam is identified as a suitable candidate. Nucleophilic and electrophilic regions of the molecules are identified using MESP, which adds to the reactivity information. It can be seen that the highest interaction energy has been obtained in the case of the Z5-graphene system, while the lowest interaction energy has been obtained in the case of the Z1-graphene system. Docking indicates that the ligands adsorbed over graphene also form stable complexes with the receptors as indicated by the high binding affinity energy values.

A Rapid Detection Method for On-site Screening of Estazolam in Beverages with Au@Ag Core-shell Nanoparticles Paper-based SERS Substrate.

Estazolam (EST) is a common sedative-hypnotic drug with a risk of abuse. Therefore, rapid on-site detection of EST is necessary to control the abuse of EST. In this paper, a fast, simple, and sensitive method is demonstrated for the detection of EST in both water and beverages, using surface-enhanced Raman spectroscopy (SERS) techniques. Au@Ag core-shell nanoparticles (NPs) assembled on the filter paper as a SERS substrate exhibit good applicability and practicality. At the same time, density functional theory (DFT) is used to assign the vibration mode of the EST molecules, which can be used as a guide for subsequent experiments. The lowest detectable concentration of EST in aqueous solution can be as low as 5 mg/L, and signal uniformity is excellent (RSD687 = 5.56%, RSD1000 = 4.35%). In addition, EST components artificially added to orange juice and pomegranate juice can be effectively detected by simple pretreatment with a minimum detection concentration as low as 10 mg/L. Therefore, this study found that the use of Au@Ag core-shell nanoparticles paper-based SERS substrate provides a quick and easy method for the detection of illegally added drugs in beverages.

[Effect of "Yinqi Guiyuan" needling on primary insomnia].

OBJECTIVE: To observe the clinical effect of "Yinqi Guiyuan" needling in the treatment of primary insomnia. METHODS: A total of 79 primary insomnia outpatients were randomly divided into treatment group (n=40) and control group (n=39). The patients in the control group were given oral Estazolam tablets once a day, for successive 4 weeks. For patients of the treatment group, Zhongwan (CV12), Xiawan (CV10), Qihai (CV6), Guanyuan (CV4), Baihui (GV20), etc., were punctured with filiform needles for 30 min. The treatment was conducted three times per week for 4 successive weeks. The sleep quality (sleeping quality, falling asleep time, sleep duration, sleep efficiency, sleep disorders, hypnotic and daytime dysfunction, 0 to 21 points) was evaluated by using Pittsburgh Sleep Quality Index (PSQI). The severity of insomnia (self-perception, sleep satisfaction, daytime function damage, sensibility change, and concern for sleep problems, 0 to 28 points) was assessed using insomnia severity index (ISI) score. The therapeutic effect was evaluated according to the PSQI score reduction rate = (pre-treatment PSQI score-post-treatment PSQI score)/pre-treatment PSQI score ×100%. RESULTS: After treatment, the total score of PSQI, ISI and the score of each item were all significantly reduced in the two groups relevant to their own pre-treatment (P<0.05). The total score, and scores of hypnotic and daytime dysfunction were significantly lower in the treatment group than in the control group (P<0.05). Of the 40 and 39 cases in the treatment and control groups, 5 (12.50%) and 4 (10.25%) were cured, 20 (50.00%) and 18 (46.15%) experienced marked improvement, 12 (30.00%) and 13 (33.33%) were effective, and 3 (7.50%) and 4 (10.25%) ineffective, with the total effective rate being 92.50% and 89.74%, respectively. No significant difference was found between the two groups in the effective rate (P>0.05). CONCLUSION: "Yinqi Guiyuan" needling and Estazolam are comparable in treatment primary insomnia, and the former is superior to the latter in avoiding hypnotic drug use and in improving daytime function.

Clinical effectiveness of Tui Na for insomnia compared with estazolam: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The purpose of this systematic review (SR) is to evaluate the effectiveness and safety of Tui Na therapy for insomnia. METHODS: Two authors separately searched PubMed, the Cochrane Library, EMBASE, SinoMed Database, China National Knowledge Infrastructure (CNKI), Wanfang Database, China Science Technology Journal Database, related SR and published protocols at the same time to find randomized controlled trials (RCTs), which compared Tui Na therapy with estazolam therapy for insomnia, from their inception to January1st 2019. Screening documents, data extraction, quality assessment of methodology and quality assessment of evidence were also conducted by two authors separately at the same time. We used Cochrane Risk of Bias tool to assess the methodological quality of included RCTs. The results of meta-analysis were made via RevMan software (5.3). The quality of evidence was assessed by on-line GRADEpro. The primary outcome: Pittsburgh Sleep Quality Index (PSQI) score, the secondary outcome: clinical effectiveness rate and the safety index: adverse events. The clinical effectiveness of these included RCTs all focused on the improvement of patients' satisfaction with sleep time and sleep quality. RESULTS: We included 22 RCTs(1,999 participants), meeting the inclusion and exclusion criteria. The assessment of methodological quality was not satisfied, in which "high risk", "unclear risk" and "low risk" all existed. The results of meta-analysis demonstrated that (1)for primary outcome, the PSQI score of Tui Na therapy was lower than that of estazolam therapy after treatment in subgroup1(Head)(MD-2.39,95%CI[-3.79,-0.98],I2 = 82%,n = 291,3 trials) and subgroup4(Abdomen)(MD-1.7,95%CI[-2.53,-0.87],I2 = 0%,n = 120,2 trials);while there was no significant difference between Tui Na therapy and estazolam therapy in subgroup2(Head and trunk)(MD-1.39,95%CI[-3.03,0.24],I2 = 90%,n = 200, 2 trials) and subgroup3(Head, trunk and extremities)(MD-0.51,95%CI[-1.53,0.5],I2 = 30%,n = 126,2 trials).(2) for secondary outcomes(the clinical effectiveness rate and safety index),the clinical effectiveness rate of Tui Na therapy was higher than that of estazolam therapy after treatment in subgroup1(Head)(RR1.21,95%CI[1.05,1.39],I2 = 26%,n = 239,3 trials), subgroup2(Head and trunk)(RR1.15,95%CI[1.08,1.23],I2 = 33%,n = 1024,10 trials) and subgroup4(Abdomen)(RR1.12,95%CI[1.01,1.23],I2 = 0%,n = 180,3 trials); while there was no significant difference between Tui Na therapy and estazolam therapy in subgroup3(Head, trunk and extremities)(RR1.03,95%CI[0.94,1.13],I2 = 28%,n = 346,4 trials).Safety index, 5 RCTs reported adverse events. Among them, only 1 RCT reported adverse event in Tui Na therapy, which was daytime drowsiness; all 5 RCTs reported adverse events in estazolam therapy, which were dry mouth, dizziness, daytime drowsiness etc. The evidence quality was generally low to very low. CONCLUSION: Tui Na therapy appeared to be superior to estazolam therapy in treating areas(head; abdomen), while there was no significant difference between Tui Na therapy and estazolam therapy in treating areas(head and trunk; head, trunk and extremities). No serious adverse event was reported in Tui Na therapy. However the methodological quality and evidence quality were not satisfied. Therefore we could not make a convincing conclusion on the effectiveness and safety of Tui Na therapy for insomnia. Practitioners should combine their experience, evidence of our review and patients' preferences to make a proper treatment. And more high quality RCTs and well-designed protocols of Tui Na therapy for insomnia are needed in the future.

Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs （Poisons.

ABSTRACT: Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs （poisons） in blood by gas chromatography-mass spectrometry （GC-MS） method. Methods Four common drugs （poisons） （dichlorvos, phorate, diazepam and estazolam） were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs （poisons） in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 µg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection （LOD）, 2LOD, limit of quantitation （LOQ） and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs （poisons） and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant （P>0.05）. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration （concentration less than 2LOQ） or low signal to noise ratio （3-15）, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs （poisons） in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.

Effect of "Yinqi Guiyuan" needling on primary insomnia / 针刺研究

OBJECTIVE: To observe the clinical effect of "Yinqi Guiyuan" needling in the treatment of primary insomnia. METHODS: A total of 79 primary insomnia outpatients were randomly divided into treatment group (n=40) and control group (n=39). The patients in the control group were given oral Estazolam tablets once a day, for successive 4 weeks. For patients of the treatment group, Zhongwan (CV12), Xiawan (CV10), Qihai (CV6), Guanyuan (CV4), Baihui (GV20), etc., were punctured with filiform needles for 30 min. The treatment was conducted three times per week for 4 successive weeks. The sleep quality (sleeping quality, falling asleep time, sleep duration, sleep efficiency, sleep disorders, hypnotic and daytime dysfunction, 0 to 21 points) was evaluated by using Pittsburgh Sleep Quality Index (PSQI). The severity of insomnia (self-perception, sleep satisfaction, daytime function damage, sensibility change, and concern for sleep problems, 0 to 28 points) was assessed using insomnia severity index (ISI) score. The therapeutic effect was evaluated according to the PSQI score reduction rate = (pre-treatment PSQI score-post-treatment PSQI score)/pre-treatment PSQI score ×100%. RESULTS: After treatment, the total score of PSQI, ISI and the score of each item were all significantly reduced in the two groups relevant to their own pre-treatment (P0.05). CONCLUSION: "Yinqi Guiyuan" needling and Estazolam are comparable in treatment primary insomnia, and the former is superior to the latter in avoiding hypnotic drug use and in improving daytime function.

Ion Abundance Ratios of Qualitative Analysis by GC-MS of 4 Common Drugs （Poisons / 法医学杂志

Objective To investigate the maximum allowable deviation of ion abundance ratios of characteristic fragment ions in common drugs （poisons） in blood by gas chromatography-mass spectrometry （GC-MS） method. Methods Four common drugs （poisons） （dichlorvos, phorate, diazepam and estazolam） were detected by GC-MS full scan mode after liquid-liquid extraction in two laboratories and under three chromatographic conditions. The deviations of ion abundance ratios of the four common drugs （poisons） in marked blood samples with concentrations of 0.5, 1.0, 2.0, 5.0 and 10.0 μg/mL were analyzed. At the same time, the false negative rates of ion abundance ratios were analyzed when the mass concentration was limit of detection （LOD）, 2LOD, limit of quantitation （LOQ） and 2LOQ, and the false positive rates of ion abundance ratios were analyzed with blank blood samples. Results Under the two laboratories, four common drugs （poisons） and three kinds of chromatography conditions, the differences in deviations of the ion abundance ratios of marked blood samples were not statistically significant （P>0.05）. More than 95% of the absolute deviations of the ion abundance ratios of the marked blood samples were within the range of ±10%, and more than 95% of the relative deviations were within the range of ±25%. In cases of low concentration （concentration less than 2LOQ） or low signal to noise ratio （3-15）, the false negative rate was less than 5% and the false positive rate was 0% when the relative deviation was greater than 50%. Conclusion The absolute deviations of ion abundance ratios of four common drugs （poisons） in marked blood samples are advised to have a determination range within ±10%, and the determination range of relative deviations within ±25%.