Displaying all 12 publications

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  1. Bujang NB, Chee CF, Heh CH, Rahman NA, Buckle MJC
    PMID: 28580889 DOI: 10.1080/19440049.2017.1336674
    Adulteration of herbal health supplements with phosphodiesterase-5 (PDE-5) inhibitors and their analogues is becoming a worldwide problem. The aim of this study was to investigate herbal and food products sold in the Malaysian market for the presence of these adulterants. Sixty-two products that claim to enhance men's sexual health were sampled between April 2014 and April 2016. These products included unregistered products seized by the Pharmacy Enforcement Division of the Ministry of Health (n = 39), products sent to the National Pharmaceutical Regulatory Agency for pre-registration testing (n = 9) and products investigated under the post-registration market surveillance programme (n = 14). The products were tested against an in-house spectral library consisting of 61 PDE-5 inhibitors and analogues using a validated liquid chromatography-mass spectrometry ion-trap-time-of-flight (LC-MS IT-TOF) method. Thirty-two (82%) of the unregistered products and two (14%) of the registered products were found to be adulterated with at least one PDE-5 inhibitor or analogue, while none of the pre-registration products contained adulterants. A total of 16 different adulterants were detected and 36% of the adulterated products contained a mixture of two or more adulterants. This study has demonstrated that the adulteration of unregistered herbal products in the Malaysian market is an alarming issue that needs to be urgently addressed by the relevant authorities.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/analysis*; Phosphodiesterase 5 Inhibitors/chemistry*
  2. Mohd Yusop AY, Xiao L, Fu S
    Forensic Sci Int, 2021 May;322:110748.
    PMID: 33711768 DOI: 10.1016/j.forsciint.2021.110748
    The presence of erectile dysfunction (ED) drugs in adulterated dietary supplements, mainly in pharmaceutical dosage forms, is frequently addressed in the literature. Little attention is given to food products despite their increasing adulteration trend. To address this knowledge gap targeted, suspected-target, and non-targeted strategies were utilised to analyse ED drugs and their analogues in powdered drink mix (PDM), honey, jelly, hard candy, and sugar-coated chewing gum using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). The method was optimised and validated using 23 target analytes, representing different ED drugs with structural similarities. The modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) extraction exhibited insignificant matrix effect (ME) within - 9.2-8.8% and provided complete coverage of target analytes with acceptable extraction recovery (RE) within 75.5-123.9%, except for carbodenafil in the PDM matrix. Based on the ME and RE performance, the analytical method was validated to analyse 25 food samples that claimed to enhance male sexual performance. The method exhibited good specificity and linearity with a limit of detection within 10-70 ng/mL and limit of quantification of 80 ng/mL. Similarly, the accuracy and precision were satisfactory within 77.4-122.0% and
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/analysis*
  3. Muin MRA, Ahmad S, Jasman MH, Aziz AFA, Ali MF, Zainuddin ZM
    Ann Fam Med, 2023;21(6):502-507.
    PMID: 38012042 DOI: 10.1370/afm.3030
    PURPOSE: Erectile dysfunction (ED) is frequently undermanaged due to communication barriers, particularly among Asian men. We looked at how ED discussion and treatment were affected by the patient's prompt sheet and the Knowledge Translation Tools in the Management of Erectile Dysfunction (LASTED).

    METHODS: We conducted a quasi-experimental study in a primary care clinic in Kedah, Malaysia involving 120 Asian men with diabetes. In the intervention group, patients were given a prompt sheet to indicate their intention to discuss or receive ED treatment, and physicians were provided with LASTED to assist with ED consultation. The control group patients received standard care from their physicians.

    RESULTS: The intervention increased the initiation of ED discussion up to 66.7% compared with 8.3% in the control group. In the intervention group, 57.5% of patients were prescribed phosphodiesterase-5 inhibitors and men with ED of moderate severity were more likely to be prescribed oral ED medication. Use of the LASTED flipchart was associated with prescription of phosphodiesterase-5 inhibitors (P = .011) and patient satisfaction with ED consultation (P

    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/therapeutic use
  4. Koon CS, Sidi H, Kumar J, Xi OW, Das S, Hatta MH, et al.
    Curr Drug Targets, 2018;19(12):1366-1377.
    PMID: 28215172 DOI: 10.2174/1389450118666170215164747
    Erectile function (EF) is a prerequisite for satisfactory sexual intercourse (SI) and central to male sexual functioning. Satisfactory SI eventually initiates orgasm - a biopsychophysiological state of euphoria - leading to a sense of bliss, enjoyment and positive mental well being. For a psychiatrist, treating ED is self-propelled to harmonize these pleasurable experiences alongside with encouragement of physical wellness and sensuality. Hence, the role of PDE-5i is pivotal in this context and constitutes a therapeutic challenge. PDE-5i work via the dopaminergic-oxytocin-nitric oxide pathway by increasing the availability of endothelial's guanosine monophosphate (GMP), immediately causing relaxation of the penile smooth muscle and an erection. The PDE-5i, like sildenafil, vardenafil and tadalafil, are effective in the treatment of ED with some benefits/ flexibilities and disadvantages compared to other treatment modalities. Prescribed PDE-5i exclusively improve EF, fostering male's self-confidence and self-esteem. Treatment failures are associated with factors such as absent (or insufficient) sexual stimulation, psychosexual conflicts and the co-existence of medical disorders. Managing ED requires dealing with underlying medical diseases, addressing other co-morbid sexual dysfunctions like premature ejaculation (PE), and educating the patient on healthy life-styles. Furthermore, by dealing with interpersonal dynamics within the couple and embracing adequate lifestyles (managing stress and revising one's sexual scripts), PDE-5i treatment benefits may be enhanced. In this review, we propose a holistic conceptual framework approach for psychiatric management of patients with ED.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/adverse effects; Phosphodiesterase 5 Inhibitors/therapeutic use*
  5. Mohd Yusop AY, Xiao L, Fu S
    Data Brief, 2019 Aug;25:104234.
    PMID: 31384643 DOI: 10.1016/j.dib.2019.104234
    This paper presents the data on the optimisation and validation of a liquid chromatography-high-resolution mass spectrometry (LC-HRMS) to establish the presence of phosphodiesterase 5 (PDE5) inhibitors and their analogues as adulterants in instant coffee premixes. The method development data covered chromatographic optimisation for better analyte separation and isomeric resolution, mass spectrometry optimisation for high sensitivity and sample preparation optimisation for high extraction recovery (RE) and low matrix effect (ME). The validation data covered specificity, linearity, range, accuracy, limit of detection, limit of quantification, precisions, ME, and RE. The optimisation and validation data presented here is related to the article: "Determination of phosphodiesterase 5 (PDE5) inhibitors in instant coffee premixes using liquid chromatography-high-resolution mass spectrometry (LC-HRMS)" Mohd Yusop et al., 2019.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors
  6. Mokhtar SU, Chin ST, Kee CL, Low MY, Drummer OH, Marriott PJ
    J Pharm Biomed Anal, 2016 Mar 20;121:188-196.
    PMID: 26808068 DOI: 10.1016/j.jpba.2016.01.034
    Application of gas chromatography-triple quadrupole mass spectrometry for identification, confirmation and quantification of 6 phosphodiesterase-5 (PDE-5) inhibitors (sildenafil, dimethylsildenafil, homosildenafil, thiosildenafil, thiodimethylsildenafil and thiohomosildenafil) in dietary supplements was investigated. The MS was operated in multiple reaction monitoring mode, for better sensitivity and selectivity. In this manner, the method is adequate to reduce background noise with less interference from co-eluting compounds in the samples. Two different ionisation techniques, electron ionisation (EI) and chemical ionisation (CI), were studied and compared. The chromatographic separation was performed on a short 10 m non-polar capillary column without any derivatisation step. This permitted fast analysis for all analogues with retention time less than 11 min, for both techniques. Use of backflushing can aid method retention time reduction and improves column maintenance. Evaluation of method validation included limit of detection (LOD), lower limit of quantitation (LLOQ), linearity, precision and recovery were performed for both EI and CI techniques. The LOD obtained varied from 0.03 to 1.50 μg/g and the LLOQ ranged from 0.10 to 5.00 μg/g. Good calibration linearity was obtained for all analogues for both techniques, with correlation coefficients (r(2)) higher than 0.99. Mean recoveries of all analogues using CI show higher values (83.4-108.8%) than that of EI (61.9-91.1%). The intra- and inter-assay precisions were evaluated for all analogues at spiked concentration of 10 μg/g and the relative standard deviation was less than 15% for both methods. These methods were then successfully applied to dietary supplement samples without prior derivatisation, confirming that the samples were adulterated with sildenafil and/or its analogues.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/chemistry
  7. Mohd Yusop AY, Xiao L, Fu S
    Talanta, 2019 Nov 01;204:36-43.
    PMID: 31357306 DOI: 10.1016/j.talanta.2019.05.078
    As a widely consumed beverage, coffee tends to be a target for intentional adulteration. This study describes the application of modified quick, easy, cheap, effective, rugged, and safe (QuEChERS) coupled to liquid chromatography-high-resolution mass spectrometry (LC-HRMS) for simultaneous screening, identification, and quantification of undeclared phosphodiesterase 5 (PDE5) inhibitors in instant coffee premixes (ICPs). The mass spectrometer was operated in auto MS/MS acquisition for simultaneous MS and MS/MS experiments. Qualitative establishments from the suspected-target screening and targeted identification processes led to an unambiguous analyte assignment from the protonated molecule ([M+H]+) precursor ion which is subsequently used for quantification of 23 targeted PDE5 inhibitors. The analytical method validation covered specificity, linearity, range, accuracy, limit of detection (LOD), limit of quantification (LOQ), precisions, matrix effect (ME), and extraction recovery (RE). The specificity was established using the optimised chromatographic separation as well as the distinguishable [M+H]+ precursor ion. The linearity of each target analyte was demonstrated with a coefficient of determination (r2) of >0.9960 over the expected range of sample concentrations. The accuracy ranged from 88.1%-119.3% with LOD and LOQ of <70 ng/mL and 80 ng/mL, respectively. Excellent precisions were established within 0.4%-9.1% of the relative standard deviation. An insignificant ME within -5.2% to +8.7% was achieved using three different strategies of chromatography, sample extraction, and sample dilution. The RE was good for all target analytes within 84.7%-123.5% except for N-desethylacetildenafil at low (53.8%) and medium (65.1%) quality control levels. The method was successfully applied to 25 samples of ICPs where 17 of them were found to be adulterated with PDE5 inhibitors and their analogues. Further quantification revealed the total amount of these adulterants ranged from 2.77 to 121.64 mg per sachet.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/analysis*
  8. Zainol M, Sidi H, Kumar J, Das S, Ismail SB, Hatta MH, et al.
    Curr Drug Targets, 2019;20(2):182-191.
    PMID: 28302034 DOI: 10.2174/1389450118666170315110902
    Throughout the world, antidepressants (AD) and phosphodiesterase-5 inhibitors (PDE-5i) are the commonly prescribed psychopharmacological agents for treating patients with co-morbid mental health problem and sexual dysfunction (SD). The serotonergic and noradrenergic ADs, although effective, are not without any SD adverse-effects, especially erectile dysfunction (ED). ED is a failure to obtain a satisfactory erection for rewarding sexual coitus during the phases of male's sexual arousal. It is recognized as an important reason why non-adherence to treatment was observed in patients who were on AD. AD intervention caused remission to some of the pre- treatment psychopathology of ED. However, in many patients, AD potentially magnified the unwanted sexual sideeffects. This made the situation challenging for the mental health professional. These challenges are based on the complexity of ED, its etiology and the associated risk factors, which further add to its AD side-effect. The neuro-psychopharmacological basis for AD treatment selection was deliberated. Bio-psycho-social interventions are recommended at two pivotal stages. Firstly, a step should be taken for proper assessment (e.g. detailed history, psychosocial and laboratory investigations); and identify few modifiable risk factors for ED and associated mental health issues. Secondly, with guidance of an algorithm pathway, a practical intervention should include strategies such as dose reduction, augmentation or changing to an AD with lesser or no sexual adverse-effects. It is recommended that bupropion and mirtazepine to be prescribed when patients develop adverse sexual effects with serotonin selective reuptake inhibitor (SSRI), serotonin norepinephrine reuptake inhibitor (SNRI) and tricyclic antidepressant (TCA). Few suggestions which may be borne in mind are revising sexual scripts and improving sexual techniques, life-style modifications, psychotherapy and other nonpharmacological approaches which may be beneficial to both patients and their partners.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/therapeutic use*
  9. Mohd Yusop AY, Xiao L, Fu S
    Drug Test Anal, 2021 May;13(5):965-976.
    PMID: 32441056 DOI: 10.1002/dta.2861
    The lucrative market of herbal remedies spurs rampant adulteration, particularly with pharmaceutical drugs and their unapproved analogues. A comprehensive screening strategy is, therefore, warranted to detect these adulterants and, accordingly, to safeguard public health. This study uses the data-dependent acquisition of liquid chromatography-quadrupole time-of-flight-mass spectrometry (LC-QTOF-MS) to screen phosphodiesterase 5 (PDE5) inhibitors in herbal remedies using suspected-target and non-targeted strategies. For the suspected-target screening, we used a library comprising 95 PDE5 inhibitors. For the non-targeted screening, we adopted top-down and bottom-up approaches to flag novel PDE5 inhibitor analogues based on common fragmentation patterns. LC-QTOF-MS was optimised and validated for capsule and tablet dosage forms using 23 target analytes, selected to represent different groups of PDE5 inhibitors. The method exhibited excellent specificity and linearity with limit of detection and limit of quantification of <40 and 80 ng/mL, respectively. The accuracy ranged from 79.0% to 124.7% with a precision of <14.9% relative standard deviation. The modified, quick, easy, cheap, effective, rugged, and safe extraction provided insignificant matrix effect within -9.1%-8.0% and satisfactory extraction recovery of 71.5%-105.8%. These strategies were used to screen 52 herbal remedy samples that claimed to enhance male sexual performance. The suspected-target screening resulted in 33 positive samples, revealing 10 target analytes and 2 suspected analytes. Systematic MS and tandem MS interrogations using the non-targeted screening returned insignificant signals, indicating the absence of potentially novel analogues. The target analytes were quantified from 0.03 to 121.31 mg per dose of each sample. The proposed strategies ensure that all PDE5 inhibitors are comprehensively screened, providing a useful tool to curb the widespread adulteration of herbal remedies.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors
  10. Cullen JF, Chung HW
    Med J Malaysia, 2010 Dec;65(4):315-6.
    PMID: 21901956
    The diagnosis of optic neuritis and particularly retrobulbar optic neuritis when atypical and not responsive to corticosteroid treatment may need to be revised. This is now especially so in male patients who should be questioned regarding their taking a phosphodiasterase-5 inhibitor in particular Viagra. The case history of such a patient is presented who sustained posterior ischaemic optic neuropathy mistaken for retrobulbar neuritis resulting in bilateral severe visual loss.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/adverse effects*
  11. Zaman Huri H, Lian Choo T, Sulaiman CZ, Mark R, Abdul Razack AH
    BMJ Open, 2014 Jul 07;4(7):e005381.
    PMID: 25001396 DOI: 10.1136/bmjopen-2014-005381
    OBJECTIVE: To investigate factors associated with demographic/clinical characteristics and drug selection in patients with erectile dysfunction (ED). The prevalence of ED is increasing worldwide. Studies have shown that ED is associated with age, lifestyle and comorbidities. However, the factors associated with patient characteristics as well as drug selection are incompletely understood.

    SETTING: A tertiary medical centre in Kuala Lumpur, Malaysia.

    PARTICIPANTS: A total of 219 patients (range 23-80 years) who had received phosphodiesterase type-5 (PDE-5) inhibitors as ED treatment were evaluated.

    INCLUSION CRITERIA: Adult patients aged ≥18 years, diagnosed with ED, and prescribed with sildenafil, tadalafil or vardenafil.

    EXCLUSION CRITERIA: Patients diagnosed with ED but who did not receive any PDE-5 inhibitor, or those with missing data.

    PRIMARY AND SECONDARY OUTCOME MEASURES: Factors associated with demographic and clinical characteristics as well as drug selection were assessed.

    RESULTS: Ischaemic heart disease (p=0.025), benign prostatic hyperplasia (p<0.001), obesity (p=0.005), lower urinary tract symptoms (LUTS) (p=0.006) and α-blockers (p<0.001) were significantly associated with elderly patients with ED. Additionally, LUTS (p=0.038) and α-blockers (p=0.008) were significantly associated with the selection of PDE-5 inhibitor.

    CONCLUSIONS: These data showed that elderly patients with ED were significantly associated with comorbidities and α-blockers, whereas LUTS and α blockers were associated with drug selection.

    Matched MeSH terms: Phosphodiesterase 5 Inhibitors/administration & dosage
  12. Mohd Yusop AY, Xiao L, Fu S
    Drug Test Anal, 2021 May;13(5):953-964.
    PMID: 32959983 DOI: 10.1002/dta.2926
    The surge in the consumption of food products containing herbal aphrodisiacs has driven their widespread adulteration. A rapid screening strategy is, therefore, warranted to curb this problem. This study established an enzyme inhibition assay to screen phosphodiesterase 5 (PDE5) inhibitors as adulterants in selected food products. Fluorescein-labelled cyclic-3',5'-guanosine monophosphate was utilised as substrates for the PDE5A1 enzyme, aided by the presence of nanoparticle phosphate-binding beads on their fluorescence polarisation. The sample preparation was optimised to improve the enzyme inhibition efficiency and applied to calculate the threshold values of six blank food matrices. The assay was validated using sildenafil, producing an IC50 of 4.2 nM. The applicability of the assay procedure was demonstrated by screening 55 distinct food samples. The results were subsequently verified using confirmatory liquid chromatography-high-resolution mass spectrometry (LC-HRMS) analysis. Altogether, 49 samples inhibited the PDE5 enzyme above the threshold values (75.7%-105.5%) and were registered as potentially adulterated samples. The remaining six samples were marked as nonadulterated with percentage inhibition below the threshold values (-3.3%-18.2%). The LC-HRMS analysis agreed with the assay results for all food products except for the instant coffee premix (ICP) samples. False-positive results were obtained for the ICP samples at 32% (8/25), due to possible PDE5 inhibition by caffeine. Contrarily, all other food samples were found to produce 0% (0/30) false-positive or false-negative results. The broad-based assay, established via a simple mix-incubate-read format, exhibited promising potential for high-throughput screening of PDE5 inhibitors in various food products, except those with naturally occurring phosphodiesterase inhibitors such as caffeine.
    Matched MeSH terms: Phosphodiesterase 5 Inhibitors
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