Cobus Gerber

A new LC–MS/MS bioanalytical method for atenolol in human plasma and milk

AIM A new sensitive LC-MS/MS method for the quantification of atenolol in human plasma and milk has been developed for clinical lactation studies. METHODS & RESULTS Atenolol and the internal standard, phenazone, were extracted from biological matrices by protein precipitation. A Phenomenex® C-18 column and gradient chromatographic conditions were used for separation of the analyte, followed by detection with MS. Stability of samples was confirmed for atenolol in human plasma and milk for up to 3 months. Linearity range of 1-800 ng/ml (r2 = 0.9995), the precision within 15% CV and the recovery of the analyte (80-100% range) were achieved. CONCLUSION A new validated analytical method for atenolol in plasma and milk was developed.

Qualitative and quantitative temporal analysis of licit and illicit drugs in wastewater in Australia using liquid chromatography coupled to mass spectrometry

AbstractThe combination of qualitative and quantitative bimonthly analysis of pharmaceuticals and illicit drugs using liquid chromatography coupled to mass spectrometry is presented. A liquid chromatography-quadrupole time of flight instrument equipped with Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) was used to qualitatively screen 346 compounds in influent wastewater from two wastewater treatment plants in South Australia over a 14-month period. A total of 100 compounds were confirmed and/or detected using this strategy, with 61 confirmed in all samples including antidepressants (amitriptyline, dothiepin, doxepin), antipsychotics (amisulpride, clozapine), illicit drugs (cocaine, methamphetamine, amphetamine, 3,4-methylenedioxymethamphetamine (MDMA)), and known drug adulterants (lidocaine and tetramisole). A subset of these compounds was also included in a quantitative method, analyzed on a liquid chromatography-triple quadrupole mass spectrometer. The use of illicit stimulants (methamphetamine) showed a clear decrease, levels of opioid analgesics (morphine and methadone) remained relatively stable, while the use of new psychoactive substances (methylenedioxypyrovalerone (MDPV) and Alpha PVP) varied with no visible trend. This work demonstrates the value that high-frequency sampling combined with quantitative and qualitative analysis can deliver. Graphical abstractTemporal analysis of licit and illicit drugs in South Australia

Investigating the correlation between wastewater analysis and roadside drug testing in South Australia.

BACKGROUND The societal impact of drug use is well known. An example is when drug-intoxicated drivers increase the burden on policing and healthcare services. METHODS This work presents the correlation of wastewater analysis (using UHPLC-MS/MS) and positive roadside drug testing results for methamphetamine, 3,4-methylenedioxymethamphetamine (MDMA) and cannabis from December 2011-December 2016 in South Australia. RESULTS Methamphetamine and MDMA showed similar trends between the data sources with matching increases and decreases, respectively. Cannabis was relatively steady based on wastewater analysis, but the roadside drug testing data started to diverge in the final part of the measurement period. CONCLUSIONS The ability to triangulate data as shown here validates both wastewater analysis and roadside drug testing. This suggests that changes in overall population drug use revealed by WWA is consistent and proportional with changes in drug-driving behaviours. The results show that, at higher levels of drug use as measured by wastewater analysis, there is an increase in drug driving in the community and therefore more strain on health services and police.

LC-HRMS suspect screening to show spatial patterns of New Psychoactive Substances use in Australia.

New Psychoactive Substances (NPS) are an ever-changing class of compounds designed to imitate the effects of current recreational drugs. Such a diverse market is difficult to assess by traditional means, while collected information can become obsolete before it is available. Wastewater-based epidemiology is one technique which can capture information on where and when NPS appear at the community level. The aim of this study was to identify NPS in wastewater samples using a suspect screening approach. Weekend samples were collected from 50 wastewater treatment plants from Australian capital cities and regional areas across all eight States and Territories and screened against a database containing almost 200 NPS. A total of 22 different NPS were found across all regional and metropolitan wastewater treatment plants. Results showed that the most detected compounds were of the cathinone class, with both Alpha-PVP and methcathinone found in every region. In addition, five different synthetic cannabinoids were detected, at least once in half of the regions analysed. Herein, we report the first comprehensive nationwide analysis of NPS and show the utility of liquid chromatography-high resolution mass spectrometry screening for delivering spatial information of the NPS being consumed in communities.

Estimation of Atenolol Transfer Into Milk and Infant Exposure During Its Use in Lactating Women

Background: Atenolol lactation information is limited, and controversy exists over the safety of its use during breastfeeding. In this study, important parameters including milk-to-plasma ratio, ratio of infant plasma to maternal plasma, infant daily dosage, and relative infant dose were investigated. The findings from this study add information to existing data about atenolol transfer in human milk. This may help guide health professionals in decision making regarding the safety of beta blockers used by mothers during breastfeeding. Research aim: The aims of the study were to quantify concentrations of atenolol in human plasma and milk, to evaluate atenolol pharmacokinetics in lactating women, and to investigate subsequent infant exposure to atenolol via mother’s milk. Methods: In this prospective, longitudinal observational study, participants were lactating mothers (N = 3), 1 to 4 months postpartum, who had been taking atenolol for therapeutic reasons, and one 4-month-old breastfed infant. Eight milk samples were collected over 24 hr at different time points, together with a single blood sample from each lactating mother and the infant, and quantified using a new sensitive liquid chromatography mass spectrometry method developed for this study. Results: Peak milk concentrations of atenolol were observed in the women at 4 hr (Tmax) after oral administration. The dose-normalized maximum concentrations (Cmax) of all patients were similar. The mean milk-to-plasma ratio of the patients who were taking 25 to 100 mg of atenolol was 8.57%. In the mother–infant pair study, the ratio (%) of infant plasma drug concentration to maternal plasma drug concentration observed (18.87%) was similar to the relative infant dose estimated (18.20%). The relative infant dose values (13.96%-18.20%) for all patients were within 10% to 25% of maternal dosage. Conclusion: Atenolol use during breastfeeding should be undertaken with some precaution. If clinically indicated, an alternate beta blocker may be preferred.

Investigating the appearance of new psychoactive substances in South Australia using wastewater and forensic data

New psychoactive substances (NPS) have increased in use and popularity worldwide. Wastewater analysis has been successfully applied to evaluate illicit drugs use within a population. However, for NPS, such an approach may be limited due to low doses of NPS combined with their ever-changing composition and usage. The dynamic nature of the NPS market means use may be opportunistic, infrequent, and with few users. Hence, the use of complementary information sources is recommended to improve the knowledge on NPS consumption. The aim of this study was to investigate the changing landscape of NPS use on a community scale by combining wastewater analysis and forensic toxicology. Forensic analysis provided specific information on NPS prevalence in post-mortem blood samples in Adelaide, South Australia over five years, while wastewater analysis showed community use over the same period. A qualitative liquid chromatography--high resolution mass spectrometry method was initially used to screen the wastewater samples. A total of 24 NPS were found: 6 in wastewater only, 13 in forensic post-mortem toxicology samples only, and 5 in both. As these results showed the presence of NPS, a targeted method was subsequently employed to quantify levels of these NPS in wastewater. Temporal trends were found in wastewater with distinct tendencies for synthetic cathinones visible over the period studied.

Transfer of rosuvastatin into breast milk: liquid chromatography–mass spectrometry methodology and clinical recommendations

Introduction Rosuvastatin reduces concentrations of total cholesterol (TC) and is used for the management of hypercholesterolemia and prevention of acute coronary syndromes. There are no published reports estimating infant exposure to rosuvastatin through breast milk. Purpose The aims of this study were to quantify concentrations of rosuvastatin in human milk and plasma from a lactating woman taking rosuvastatin and to investigate potential infant exposure. Materials and methods A 38-year-old breastfeeding mother was commenced on rosuvastatin 20 mg daily for secondary prevention of an acute coronary syndrome. Eight maternal breast milk samples and a single plasma sample were collected over a 24-hour period. The samples were quantified using a sensitive liquid chromatography–mass spectrometry (LC-MS/MS) method. Results The average concentration of rosuvastatin in breast milk was 30.84 ng/mL, and a peak concentration of 58.59 ng/mL occurred at 17 hours after oral administration. Although the milk-to-plasma (M/P) ratio was 16.49 at 14 hours, the theoretical infant dosage (TID) and relative infant dose (RID) were 0.005 mg/kg/day and 1.50%, respectively. Conclusion The findings suggest that only small amounts of rosuvastatin pass into breast milk. Should the maternal condition necessitate treatment, consideration could be given to the use of rosuvastatin during breastfeeding provided the infant is monitored.

Wastewater analysis shows a large decrease in oxycodone use in Adelaide

TO THE EDITOR: In Adelaide, which comprises 78% of the population of South Australia, municipal wastewater has been subject to bimonthly analysis since 2009 to measure trends in substance use. Beginning in October 2015, there was a precipitous decrease in the detection of oxycodone residues in wastewater samples (Box). This decreasewas counter to the long term trend of increasing amounts of this opioid in previous samples. Prescribing data show a continuing increase in the use of prescription opioid analgesics (POAs), including oxycodone, nationally and in SA, during the period between 1992 and 2011. There is a strong relationship between the amount of POAs used in a community and the amount of harm from opioid dependence and overdose.

A prospective study of mediating cognitive mechanisms in impulsive alcohol use by adolescents

Abstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, Australiapresented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, AustraliaAbstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, AustraliaAbstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, AustraliaAbstract presented at the Australasian Professional Society on Alcohol and other Drugs Conference 2013, 24-27 November 2013, Brisbane, Australia